肾上腺素受体、L型钙通道阻断剂降压及改善下尿路综合征新策略
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摘要
原发性高血压是由多种遗传和环境因素交互作用引起的一类复杂疾病。我国现有高血压患者2亿人,用于高血压的医疗费达366亿元。临床研究表明,平均降低收缩压10mm Hg、舒张压5mm Hg,脑卒中发生危险下降40%-50%,冠心病发生危险下降15%-20%,心力衰竭发生危险减少50%。因此,有效降低高血压患者的血压水平,对预防其并发症具有十分重要的作用。高血压药物治疗中出现相当程度的个体差异。MATH试验显示,单独使用硝苯地平缓释剂治疗高血压的有效率为76%。造成这种药物治疗个体差异的原因还不完全清楚,目前认为有其遗传学基础。研究表明,除了编码药物靶标和主要代谢酶的基因以外,参与调解血压的候选基因可能也对降压药物个体间疗效差异产生影响。交感神经系统在原发性高血压发病过程中起到重要作用,其主要作用途径是通过儿茶酚胺类物质作用于G蛋白偶联α和β肾上腺素受体。研究发现,高血压患者的心血管组织会出现交感神经功能上调,并出现不同类型的肾上腺素受体分布及密度的平衡发生变化。在中老年人群中,高血压常和下尿路综合征(良性前列腺增生是其中男性患者的主要诱因)并存,增加了治疗的难度,并使患者的生活质量进一步下降,个人和社会负担进一步加重。中国人群中65岁以上男性同时患有高血压和中重度下尿路症状的患者达42.7%。高血压可能增加患者下尿路症状的发病风险。目前临床上这两种疾病状态通常分别由心血管内科和泌尿科分别进行治疗,往往顾此失彼,达不到满意的疗效和明显改善患者生活质量的目的。因此,研究影响抗高血压药物治疗的遗传因素,以及为临床综合治疗高血压及其合并的下尿路综合征提供个体化治疗依据,具有重要的临床价值和公共卫生学意义。
本研究首先开展肾上腺素受体基因多态性与L型钙通道阻断剂硝苯地平降血压疗效的相关性研究,在其主要发现的基础上进一步开展L型钙通道阻断剂氨氯地平联合α1肾上腺素受体拮抗剂特拉唑嗪降血压和改善下尿路功能紊乱作用的动物试验探索,并设计随机、对照、双盲临床试验,对L型钙通道阻断剂氨氯地平联合α1肾上腺素受体拮抗剂特拉唑嗪降血压和改善下尿路综合征的疗效和安全性进一步验证。
1、肾上腺素受体多态性与硝苯地平降压疗效的相关性研究
目的:研究α1A肾上腺素受体Arg347Cys和β2肾上腺素受体Arg16Gly和Gln27Glu多态性是否影响硝苯地平控释片的降血压疗效。
方法:符合入选标准的中国安徽高血压患者(收缩压140-200mmHg和舒张压＜115mmHg或收缩压＜200mmHg和舒张压90-115mmHg)接受硝苯地平控释片30 mg口服治疗15天,每天1次。采用Taqman方法检测α1A受体基因T1475C(Arg347Cys)多态性和β2受体基因A265G(Arg16Gly)及C298G(Gln27Glu)基因多态性。采用高效液相方法紫外条件测定第16天硝苯地平稳态血药浓度。采用多元线性回归方法分析447名患者基因多态性与硝苯地平控释片降压疗效的关系。
结果:在校正了重要的协变量后,与携带α1A受体基因Arg347Arg基因型的患者比较,携带347Cys等位子(Arg347Cys/Cys347Cys)的患者收缩压降低更为显著(adjustedβ(se)=4.1(1.5),P=0.006),但是舒张压的下降没有达到统计学上的显著性水平(adjustedβ(se)=1.2(0.8),P=0.101)。然而,不管校正重要的协变量前后,没有发现β2受体基因两个多态性位点与血压降低水平的相关性。
结论及提示:我们的研究发现,α1A受体基因Arg347Cys多态性可能对预测中国高血压患者硝苯地平控释片的降压反应具有一定价值。这一发现提示L型钙通道可能与α肾上腺素受体在血压调节方面存在交互作用,而L型钙通道阻断剂与α肾上腺素受体拮抗剂在血压控制方面也可能存在机制的互补。2、L型钙通道阻断剂联合α1受体拮抗剂对高血压大鼠血压及对下尿路功能紊乱大鼠尿流动力学改善作用试验
目的:基于研究1的发现,同时通过文献调研发现,高血压和下尿路综合征常同时发生于老年人群中,L型钙通道对调节下尿路功能也有重要作用,L型钙通道阻断剂对改善某些下尿路症状,如膀胱过度活动症状也有作用,而α1肾上腺素受体拮抗剂同时具有抗高血压和改善下尿路综合征两方面的适应症。本部分动物研究在以上发现和提示的基础上进一步探索L型钙通道阻断剂单独或者与α肾上腺素受体拮抗剂联用是否会同时有效控制这两种疾病状态。包括:研究L型钙通道阻断剂氨氯地平与α1受体拮抗剂特拉唑嗪组合对二肾一夹型高血压模型大鼠的降血压作用;研究氨氯地平单用,或者联合特拉唑嗪,对良性前列腺增生大鼠和逼尿肌不稳定大鼠尿动力学的改善作用。
方法:
1、两肾一夹法造肾性高血压大鼠模型。成模大鼠按照体重和血压半随机分组,即:模型组、氨氯地平组(0.5 mg/kg)、特拉唑嗪组(0.4 mg/kg)、氨氯地平联合特拉唑嗪组(0.5+0.4 mg/kg)。另设假手术对照组(行手术但不结扎肾动脉)。各组连续灌胃给药28天,模型组和假手术对照组给予等容生理盐水。采用尾动脉无创血压测定仪测量给药前及给药后第1、2、3、4周各组大鼠血压变化,观察氨氯地平+特拉唑嗪对高血压大鼠血压的影响;
2、雄性Sprague-Dawley大鼠皮下注射睾酮(0.5 mg/每只,连续21天)诱导产生良性前列腺增生模型,雌性Sprague-Dawley大鼠膀胱出口不完全结扎6周诱导产生逼尿肌不稳定模型。模型大鼠随机分组后分别给予不同剂量的氨氯地平、特拉唑嗪或者氨氯地平联合特拉唑嗪,连续14天。末次给药后,双腔套管经膀胱顶部插入膀胱中,生理记录仪记录大鼠尿动力学指标,并测定膀胱指数和前列腺指数,观察药物对上述指标的改善作用。
结果:
1、与高血压模型组大鼠比较,氨氯地平组和特拉唑嗪组收缩压和舒张压均显著下降(P＜0.05或P＜0.01);氨氯地平联合特拉唑嗪组与氨氯地平或特拉唑嗪组比较,收缩压和舒张压下降更为显著(P＜0.05或P＜0.01);
2、与良性前列腺增生模型组大鼠比较,氨氯地平0.5,1和3 mg/kg显著降低良性前列腺增生大鼠的膀胱指数,排尿压阈值和排尿压峰值,并显著其延长排尿间隔时间。氨氯地平0.5 mg/kg联合特拉唑嗪0.4 mg/kg对良性前列腺增生大鼠和逼尿肌不稳定大鼠尿动力学的改善最为显著,与两药单独使用比较,进一步降低了其膀胱指数,排尿压阈值和排尿压峰值,并进一步延长了其排尿间隔时间,与特拉唑嗪1 mg/kg作用相当。与模型组比较,氨氯地平0.5 mg/kg联合特拉唑嗪0.4 mg&g显著降低了逼尿肌不稳定大鼠的非排尿性膀胱收缩频率(2.0/4.5,P＜0.01)。
结论及提示:1、氨氯地平联合特拉唑嗪可有效降低高血压模型大鼠血压,并显著优于两药单独使用;2、氨氯地平可改善良性前列腺增生和逼尿肌不稳定大鼠的下尿路功能紊乱症状。这一研究结果支持L型钙通道阻断剂与α1受体拮抗剂联合降低高血压的加性效应,并提示氨氯地平和特拉唑嗪低剂量的联合使用具有治疗下尿路综合征的临床潜力,并可能特别适用于具有膀胱过度活动的患者。
3、L型钙通道阻断剂联合α1受体拮抗剂降血压和改善下尿路综合征的随机、对照、双盲临床试验
目的:高血压和下尿路综合征常同时发生于老年男性中。为进一步验证研究2的发现,我们继续将氨氯地平和特拉唑嗪作为研究用药,通过本临床实验来研究高血压合并下尿路综合征时L型钙通道阻断剂联合α1受体拮抗剂的疗效与安全性。
方法:355名患有1-2期原发性高血压合并下尿路综合征[定义为国际前列腺症状评分,International Prostate Symptom Score(IPSS)≥10]的男性患者随机分入2 mg特拉唑嗪治疗组(n=117)、5 mg氨氯地平治疗组(n=119)或5 mg氨氯地平加2 mg特拉唑嗪治疗组(n=119),各组每天服药一次,共28天。本研究的主要疗效终点是国际前列腺症状评分的总评分和亚评分以及血压变化。采用意向性治疗(intention to treat,ITT)人群数据集进行分析。本试验已在ClinicalTrials.gov网站注册(No.NCT00693199)。
结果:治疗28天后,与特拉唑嗪或氨氯地平组比较,氨氯地平联合特拉唑嗪组达到最佳的血压降低水平(25.2±15.7 mmHg/11.9±16.3 mmHg或21.8±13.9 mmHg,P＜0.01或P＜0.05),与特拉唑嗪组比较,血压控制率显著升高(73.1%/36.8%,P＜0.001)。与特拉唑嗪组比较,氨氯地平联合特拉唑嗪组改善刺激性症状亚评分有效率更高(53.8%/39.3%,P＜0.05);与氨氯地平组比较,联合用药组改善生活质量评分作用更为显著(1.4±1.1/1.1±1.1,P＜0.05),改善生活质量评分有效率也更高(47.1%/33.6%,P＜0.05)。三个治疗组的患者均对药物耐受良好。
结论及提示:本次的4周随机对照双盲试验显示,中国男性高血压合并下尿路综合征患者中,较低剂量的氨氯地平联合特拉唑嗪可能是一种安全和有效的同时控制这两种疾病的药物疗法,特别是对具有突出的膀胱过度活动的患者,印证了研究2的发现。
It is widely recognized that essential hypertension is a complex trait resulting from the interaction of environmental and genetic factors.It affects about 0.2 billion individuals in China and in 2008,a total of 0.266 billion Renmingbi were expended on the treatment of hypertension.Previous clinical trials have demonstrated that an average reduction of 10 mm Hg in systolic blood pressure or 5 mm Hg in diastolic blood pressure is associated with a 40-50%reduction in stroke,15-20%in coronary artery disease,and 50%in congestive heart failure.Thus,the effective reduction in blood pressure plays an important role to prevent it's related complications.However, considerable inter-individual variation was observed in the treatment of hypertension. MATH trial showed that responsive rate of nifedipine GITS on hypertension is 76%. The mechanisms underlying such inter-individual variation are yet unclear.One of the possible explanation is the individuals have different genetic background. Besides those encoding the target proteins and the key metabolic enzymes,genes involving in the regulation of blood pressure may also contribute to such inter-individual variation in antihypertensive treatment.The sympathetic nervous system plays an important role in the pathogenesis of essential hypertension,mainly through the catecholamines acting on G protein-coupledαandβadrenoceptors.A chronic increase in the sympathetic functions as well as the alterations in the balance of adrenoceptors in cardiovascular tissues is found in many hypertensive patients.In old population,hypertension and lower urinary tract symptoms are the common comorbid conditions,both of which may be caused by increased overactivity of the sympathetic system.This makes it more difficult to treat these patients properly and efficiently.Furthermore,it will reduce the quality of life of those patients and increase the economical burden individually and socially.In Chinese male population aged more than 65 years,42.7%suffer from hypertension and lower urinary tract symptoms simultaneously.Hypertension may increase the risk of developing lower urinary tract symptoms.Given the high comorbidity of hypertension and LUTS,it is important to consider and investigate therapeutic regiment that can effectively and safely manage both conditions in a certain patient, rather than treating the two conditions separately.Based on these evidences,it is valuable to study the genetic factors underlying the antihypertensive treatment and to find more ways and personalized medications for effectively treating hypertension and the co-existing lower urinary tract symptoms.
This study aimed to 1) evaluate whether the polymorphisms in theα1A andβ2 adrenoceptor genes were associated with the antihypertensive effects of nifedipine in Chinese population;2) investigate the efficiacy of the L-type calcium channel blocker amlodipine combined withα1 adrenergic antagonist terazosin on the simultaneous treatment of hypertension and lower urinary tract disorder in model rats;3) by applying a randomized,double-blind clinical trial,evaluate the efficacy and safety of those two drugs used in combination on the treatment of hypertension and lower urinary tract symptoms.
1.Association between Arg347Cys polymorphism ofα1A-adrenoceptor gene, Arg16Giy and Gln27Glu polymorphisms of Beta 2 adrenoceptor gene and blood pressure lowering effect of nifedipine
[Aims]:To investigate whether polymorphisms in theα1A andβ2 adrenoceptor genes influence antihypertensive effect of nifedipine GITS.[Methods]:Hypertensive patients,aged 35-60 years old,not taking antihypertensive medications for 4 weeks prior to this study,received daily treatment with an oral dosage of 30 mg nifedipine GITS for 16 days.Genotypes of the Arg347Cys polymorphism in theα1A-adrenoceptor gene,Arg16Gly and Gln27Glu polymorphisms in theβ2-adrenoceptor gene were determined by TaqMan SNP genotyping assay.The 16~(th) day steady state plasma concentration of nifedipine was measured using high performance liquid chromatography with ultraviolet detection.Multivariate linear regression was performed in a total of 447 patients to evaluate the impacts of these polymorphisms on the blood pressure response to nifedipine GITS.
[Results]:1) Patients carrying the 347Cys allele of theα1A-adrenoceptor gene had a greater systolic blood pressure reduction than those carrying two Arg347 alleles of theα1A-adrenoceptor gene(27.3±15.5mmHg versus 32.5±14.0mmHg,P=0.006).2) Diastolic blood pressure reduction was not associated with the Arg347Cys polymorphism in theα1A-adrenoceptor gene;3) No significant associations were observed between blood pressure reduction and two polymorphisms in theβ2-adrenoceptor gene.
[Conclusion]:The Arg347Cys polymorphism in theα1A-adrenoceptor gene may predict the blood pressure response to nifedipine GITS in Chinese hypertensive patients.
2.Effects of L-type calcium channel blocker amlodipine or combined withα1 adrenergic antagonist terazosin on hypertension and lower urinary tract disorder in rat models
[Aims]:To investigate the blood pressure lowering effects of amlodipine combined with terazosin in hypertension rat model and to investigate the effects of amlodipine, alone or combined with terazosin on urodynamics in rats with benign prostatic hyperplasia(BPH) and in female rats with detrusor instability(DI).[Method]:Two kidney 1 clip operation was conducted to induce hypertensive rat model.Model rats were semi-randomly assigned to four groups according to their body weight and blood pressure level:Model control group,amlodipine group(0.5 mg/kg),terazosin group(0.4 mg/kg) and amlodipine plus terazosin group(0.5 + 0.4 mg/kg).All the rats were intragastrically administered with assigned drugs for 28 days. Non-invasive blood pressure measurement was conducted in week 1,2,3 and 4. Rat models of BPH were induced by subcutaneous injection of testosterone(0.5 mg per rat for 21 days).Female rat models of DI were induced by partial bladder outlet ligation for 6 weeks.Model rats were intragastrically administered with assigned drugs(amlodipine,terazosin or combination of these two drugs) for 14 days in the three experiments.Continuous cystometry was performed under urethane anesthesia. [Results]:1) Systolic blood pressure(SBP) and diastolic blood pressure(DBP) in model rats were significantly increased at each timepoint.SBP and DBP in amlodipine and terazosin group were all significantly decreased.Compared with the two monotherapy group,the amlodipine plus terazosin group reached the greatest reduction on SBP and DBP.2) Amlodipine 0.5,1 and 3 mg/kg significantly decreased bladder index(BI),threshold pressure(TP),micturition pressure(MP) and significantly increased inter-micturition duration(IMD) in BPH rats.Moreover, amlodipine 0.5 mg/kg plus terazosin 0.4 mg/kg obtained the greatest improvements in all urodynamic parameters and reported greater decreased BI,TP,MP and greater increased IMD compared to either of the two drugs used alone in BPH and DI rats and showed similar efficacy compared to terazosin 1 mg/kg.The combination treatment also reached greater decreased nonvoiding bladder contraction(NVC) in DI rats.
[Conclusions]:1) Amlodipine plus terazosin could efficiently decrease blood pressure in model rats,which showed more advantage on blood pressure lowering effects than amlodipine alone or terazosin alone.2) Amlodipine or combined with terazosin may have a potential for alleviating lower urinary tract symptoms(LUTS). Meanwhile,the combination therapy appears to be more suitable for LUTS with predominant irritative symptoms.
3.Efficacy of combined amlodipine and terazosin therapy in male hypertensive patients with lower urinary tract symptoms:a randomized,double-blind clinical trial
[Aims]:Based on the findings in the second part of the study,this trial was to investigate the therapeutic efficacy and safety of amlodipine alone or in combination with terazosin for the presence of hypertension.
[Methods]:A total of 355 patients with Stage 1 or 2 hypertension and LUTS(as defined by an International Prostate Symptom Score of≥10) were randomly assigned to receive 2 mg of terazosin(n=117),5 mg of amlodipine(n=119),or 5 mg of amlodipine plus 2 mg of terazosin(n=119) once daily for a total of 28 days.The primary outcomes were a reduction in the total and subscores of the International Prostate Symptom Score and blood pressure.Analyses were performed by intention to treat.This trial is registered with ClinicalTrials.gov(No.NCT00693199).
[Results]:At day 28 of the trial,the amlodipine plus terazosin group achieved the greatest blood pressure control compared with either the terazosin group(P＜0.01) or amlodipine group(P＜0.05).The amlodipine plus terazosin group also demonstrated comparable efficacy in lowering the total International Prostate Symptom Score and significant improvement in the presence of overactive bladder compared with the terazosin group(P＜0.05) and significant improvement in quality of life compared with the amlodipine group(P＜0.05).All 3 treatment regimens were well tolerated by the study patients.
[Conclusions]:The results of this 4-week,double-blind,randomized trial have demonstrated that in Chinese male hypertensive patients with LUTS,low-dose amlodipine plus terazosin therapy appears to be a safe and effective combination therapy to control both conditions,especially for those with predominant overactive bladder symptoms.
本研究首先开展肾上腺素受体基因多态性与L型钙通道阻断剂硝苯地平降血压疗效的相关性研究,在其主要发现的基础上进一步开展L型钙通道阻断剂氨氯地平联合α1肾上腺素受体拮抗剂特拉唑嗪降血压和改善下尿路功能紊乱作用的动物试验探索,并设计随机、对照、双盲临床试验,对L型钙通道阻断剂氨氯地平联合α1肾上腺素受体拮抗剂特拉唑嗪降血压和改善下尿路综合征的疗效和安全性进一步验证。
1、肾上腺素受体多态性与硝苯地平降压疗效的相关性研究
目的:研究α1A肾上腺素受体Arg347Cys和β2肾上腺素受体Arg16Gly和Gln27Glu多态性是否影响硝苯地平控释片的降血压疗效。
方法:符合入选标准的中国安徽高血压患者(收缩压140-200mmHg和舒张压＜115mmHg或收缩压＜200mmHg和舒张压90-115mmHg)接受硝苯地平控释片30 mg口服治疗15天,每天1次。采用Taqman方法检测α1A受体基因T1475C(Arg347Cys)多态性和β2受体基因A265G(Arg16Gly)及C298G(Gln27Glu)基因多态性。采用高效液相方法紫外条件测定第16天硝苯地平稳态血药浓度。采用多元线性回归方法分析447名患者基因多态性与硝苯地平控释片降压疗效的关系。
结果:在校正了重要的协变量后,与携带α1A受体基因Arg347Arg基因型的患者比较,携带347Cys等位子(Arg347Cys/Cys347Cys)的患者收缩压降低更为显著(adjustedβ(se)=4.1(1.5),P=0.006),但是舒张压的下降没有达到统计学上的显著性水平(adjustedβ(se)=1.2(0.8),P=0.101)。然而,不管校正重要的协变量前后,没有发现β2受体基因两个多态性位点与血压降低水平的相关性。
结论及提示:我们的研究发现,α1A受体基因Arg347Cys多态性可能对预测中国高血压患者硝苯地平控释片的降压反应具有一定价值。这一发现提示L型钙通道可能与α肾上腺素受体在血压调节方面存在交互作用,而L型钙通道阻断剂与α肾上腺素受体拮抗剂在血压控制方面也可能存在机制的互补。2、L型钙通道阻断剂联合α1受体拮抗剂对高血压大鼠血压及对下尿路功能紊乱大鼠尿流动力学改善作用试验
目的:基于研究1的发现,同时通过文献调研发现,高血压和下尿路综合征常同时发生于老年人群中,L型钙通道对调节下尿路功能也有重要作用,L型钙通道阻断剂对改善某些下尿路症状,如膀胱过度活动症状也有作用,而α1肾上腺素受体拮抗剂同时具有抗高血压和改善下尿路综合征两方面的适应症。本部分动物研究在以上发现和提示的基础上进一步探索L型钙通道阻断剂单独或者与α肾上腺素受体拮抗剂联用是否会同时有效控制这两种疾病状态。包括:研究L型钙通道阻断剂氨氯地平与α1受体拮抗剂特拉唑嗪组合对二肾一夹型高血压模型大鼠的降血压作用;研究氨氯地平单用,或者联合特拉唑嗪,对良性前列腺增生大鼠和逼尿肌不稳定大鼠尿动力学的改善作用。
方法:
1、两肾一夹法造肾性高血压大鼠模型。成模大鼠按照体重和血压半随机分组,即:模型组、氨氯地平组(0.5 mg/kg)、特拉唑嗪组(0.4 mg/kg)、氨氯地平联合特拉唑嗪组(0.5+0.4 mg/kg)。另设假手术对照组(行手术但不结扎肾动脉)。各组连续灌胃给药28天,模型组和假手术对照组给予等容生理盐水。采用尾动脉无创血压测定仪测量给药前及给药后第1、2、3、4周各组大鼠血压变化,观察氨氯地平+特拉唑嗪对高血压大鼠血压的影响;
2、雄性Sprague-Dawley大鼠皮下注射睾酮(0.5 mg/每只,连续21天)诱导产生良性前列腺增生模型,雌性Sprague-Dawley大鼠膀胱出口不完全结扎6周诱导产生逼尿肌不稳定模型。模型大鼠随机分组后分别给予不同剂量的氨氯地平、特拉唑嗪或者氨氯地平联合特拉唑嗪,连续14天。末次给药后,双腔套管经膀胱顶部插入膀胱中,生理记录仪记录大鼠尿动力学指标,并测定膀胱指数和前列腺指数,观察药物对上述指标的改善作用。
结果:
1、与高血压模型组大鼠比较,氨氯地平组和特拉唑嗪组收缩压和舒张压均显著下降(P＜0.05或P＜0.01);氨氯地平联合特拉唑嗪组与氨氯地平或特拉唑嗪组比较,收缩压和舒张压下降更为显著(P＜0.05或P＜0.01);
2、与良性前列腺增生模型组大鼠比较,氨氯地平0.5,1和3 mg/kg显著降低良性前列腺增生大鼠的膀胱指数,排尿压阈值和排尿压峰值,并显著其延长排尿间隔时间。氨氯地平0.5 mg/kg联合特拉唑嗪0.4 mg/kg对良性前列腺增生大鼠和逼尿肌不稳定大鼠尿动力学的改善最为显著,与两药单独使用比较,进一步降低了其膀胱指数,排尿压阈值和排尿压峰值,并进一步延长了其排尿间隔时间,与特拉唑嗪1 mg/kg作用相当。与模型组比较,氨氯地平0.5 mg/kg联合特拉唑嗪0.4 mg&g显著降低了逼尿肌不稳定大鼠的非排尿性膀胱收缩频率(2.0/4.5,P＜0.01)。
结论及提示:1、氨氯地平联合特拉唑嗪可有效降低高血压模型大鼠血压,并显著优于两药单独使用;2、氨氯地平可改善良性前列腺增生和逼尿肌不稳定大鼠的下尿路功能紊乱症状。这一研究结果支持L型钙通道阻断剂与α1受体拮抗剂联合降低高血压的加性效应,并提示氨氯地平和特拉唑嗪低剂量的联合使用具有治疗下尿路综合征的临床潜力,并可能特别适用于具有膀胱过度活动的患者。
3、L型钙通道阻断剂联合α1受体拮抗剂降血压和改善下尿路综合征的随机、对照、双盲临床试验
目的:高血压和下尿路综合征常同时发生于老年男性中。为进一步验证研究2的发现,我们继续将氨氯地平和特拉唑嗪作为研究用药,通过本临床实验来研究高血压合并下尿路综合征时L型钙通道阻断剂联合α1受体拮抗剂的疗效与安全性。
方法:355名患有1-2期原发性高血压合并下尿路综合征[定义为国际前列腺症状评分,International Prostate Symptom Score(IPSS)≥10]的男性患者随机分入2 mg特拉唑嗪治疗组(n=117)、5 mg氨氯地平治疗组(n=119)或5 mg氨氯地平加2 mg特拉唑嗪治疗组(n=119),各组每天服药一次,共28天。本研究的主要疗效终点是国际前列腺症状评分的总评分和亚评分以及血压变化。采用意向性治疗(intention to treat,ITT)人群数据集进行分析。本试验已在ClinicalTrials.gov网站注册(No.NCT00693199)。
结果:治疗28天后,与特拉唑嗪或氨氯地平组比较,氨氯地平联合特拉唑嗪组达到最佳的血压降低水平(25.2±15.7 mmHg/11.9±16.3 mmHg或21.8±13.9 mmHg,P＜0.01或P＜0.05),与特拉唑嗪组比较,血压控制率显著升高(73.1%/36.8%,P＜0.001)。与特拉唑嗪组比较,氨氯地平联合特拉唑嗪组改善刺激性症状亚评分有效率更高(53.8%/39.3%,P＜0.05);与氨氯地平组比较,联合用药组改善生活质量评分作用更为显著(1.4±1.1/1.1±1.1,P＜0.05),改善生活质量评分有效率也更高(47.1%/33.6%,P＜0.05)。三个治疗组的患者均对药物耐受良好。
结论及提示:本次的4周随机对照双盲试验显示,中国男性高血压合并下尿路综合征患者中,较低剂量的氨氯地平联合特拉唑嗪可能是一种安全和有效的同时控制这两种疾病的药物疗法,特别是对具有突出的膀胱过度活动的患者,印证了研究2的发现。
It is widely recognized that essential hypertension is a complex trait resulting from the interaction of environmental and genetic factors.It affects about 0.2 billion individuals in China and in 2008,a total of 0.266 billion Renmingbi were expended on the treatment of hypertension.Previous clinical trials have demonstrated that an average reduction of 10 mm Hg in systolic blood pressure or 5 mm Hg in diastolic blood pressure is associated with a 40-50%reduction in stroke,15-20%in coronary artery disease,and 50%in congestive heart failure.Thus,the effective reduction in blood pressure plays an important role to prevent it's related complications.However, considerable inter-individual variation was observed in the treatment of hypertension. MATH trial showed that responsive rate of nifedipine GITS on hypertension is 76%. The mechanisms underlying such inter-individual variation are yet unclear.One of the possible explanation is the individuals have different genetic background. Besides those encoding the target proteins and the key metabolic enzymes,genes involving in the regulation of blood pressure may also contribute to such inter-individual variation in antihypertensive treatment.The sympathetic nervous system plays an important role in the pathogenesis of essential hypertension,mainly through the catecholamines acting on G protein-coupledαandβadrenoceptors.A chronic increase in the sympathetic functions as well as the alterations in the balance of adrenoceptors in cardiovascular tissues is found in many hypertensive patients.In old population,hypertension and lower urinary tract symptoms are the common comorbid conditions,both of which may be caused by increased overactivity of the sympathetic system.This makes it more difficult to treat these patients properly and efficiently.Furthermore,it will reduce the quality of life of those patients and increase the economical burden individually and socially.In Chinese male population aged more than 65 years,42.7%suffer from hypertension and lower urinary tract symptoms simultaneously.Hypertension may increase the risk of developing lower urinary tract symptoms.Given the high comorbidity of hypertension and LUTS,it is important to consider and investigate therapeutic regiment that can effectively and safely manage both conditions in a certain patient, rather than treating the two conditions separately.Based on these evidences,it is valuable to study the genetic factors underlying the antihypertensive treatment and to find more ways and personalized medications for effectively treating hypertension and the co-existing lower urinary tract symptoms.
This study aimed to 1) evaluate whether the polymorphisms in theα1A andβ2 adrenoceptor genes were associated with the antihypertensive effects of nifedipine in Chinese population;2) investigate the efficiacy of the L-type calcium channel blocker amlodipine combined withα1 adrenergic antagonist terazosin on the simultaneous treatment of hypertension and lower urinary tract disorder in model rats;3) by applying a randomized,double-blind clinical trial,evaluate the efficacy and safety of those two drugs used in combination on the treatment of hypertension and lower urinary tract symptoms.
1.Association between Arg347Cys polymorphism ofα1A-adrenoceptor gene, Arg16Giy and Gln27Glu polymorphisms of Beta 2 adrenoceptor gene and blood pressure lowering effect of nifedipine
[Aims]:To investigate whether polymorphisms in theα1A andβ2 adrenoceptor genes influence antihypertensive effect of nifedipine GITS.[Methods]:Hypertensive patients,aged 35-60 years old,not taking antihypertensive medications for 4 weeks prior to this study,received daily treatment with an oral dosage of 30 mg nifedipine GITS for 16 days.Genotypes of the Arg347Cys polymorphism in theα1A-adrenoceptor gene,Arg16Gly and Gln27Glu polymorphisms in theβ2-adrenoceptor gene were determined by TaqMan SNP genotyping assay.The 16~(th) day steady state plasma concentration of nifedipine was measured using high performance liquid chromatography with ultraviolet detection.Multivariate linear regression was performed in a total of 447 patients to evaluate the impacts of these polymorphisms on the blood pressure response to nifedipine GITS.
[Results]:1) Patients carrying the 347Cys allele of theα1A-adrenoceptor gene had a greater systolic blood pressure reduction than those carrying two Arg347 alleles of theα1A-adrenoceptor gene(27.3±15.5mmHg versus 32.5±14.0mmHg,P=0.006).2) Diastolic blood pressure reduction was not associated with the Arg347Cys polymorphism in theα1A-adrenoceptor gene;3) No significant associations were observed between blood pressure reduction and two polymorphisms in theβ2-adrenoceptor gene.
[Conclusion]:The Arg347Cys polymorphism in theα1A-adrenoceptor gene may predict the blood pressure response to nifedipine GITS in Chinese hypertensive patients.
2.Effects of L-type calcium channel blocker amlodipine or combined withα1 adrenergic antagonist terazosin on hypertension and lower urinary tract disorder in rat models
[Aims]:To investigate the blood pressure lowering effects of amlodipine combined with terazosin in hypertension rat model and to investigate the effects of amlodipine, alone or combined with terazosin on urodynamics in rats with benign prostatic hyperplasia(BPH) and in female rats with detrusor instability(DI).[Method]:Two kidney 1 clip operation was conducted to induce hypertensive rat model.Model rats were semi-randomly assigned to four groups according to their body weight and blood pressure level:Model control group,amlodipine group(0.5 mg/kg),terazosin group(0.4 mg/kg) and amlodipine plus terazosin group(0.5 + 0.4 mg/kg).All the rats were intragastrically administered with assigned drugs for 28 days. Non-invasive blood pressure measurement was conducted in week 1,2,3 and 4. Rat models of BPH were induced by subcutaneous injection of testosterone(0.5 mg per rat for 21 days).Female rat models of DI were induced by partial bladder outlet ligation for 6 weeks.Model rats were intragastrically administered with assigned drugs(amlodipine,terazosin or combination of these two drugs) for 14 days in the three experiments.Continuous cystometry was performed under urethane anesthesia. [Results]:1) Systolic blood pressure(SBP) and diastolic blood pressure(DBP) in model rats were significantly increased at each timepoint.SBP and DBP in amlodipine and terazosin group were all significantly decreased.Compared with the two monotherapy group,the amlodipine plus terazosin group reached the greatest reduction on SBP and DBP.2) Amlodipine 0.5,1 and 3 mg/kg significantly decreased bladder index(BI),threshold pressure(TP),micturition pressure(MP) and significantly increased inter-micturition duration(IMD) in BPH rats.Moreover, amlodipine 0.5 mg/kg plus terazosin 0.4 mg/kg obtained the greatest improvements in all urodynamic parameters and reported greater decreased BI,TP,MP and greater increased IMD compared to either of the two drugs used alone in BPH and DI rats and showed similar efficacy compared to terazosin 1 mg/kg.The combination treatment also reached greater decreased nonvoiding bladder contraction(NVC) in DI rats.
[Conclusions]:1) Amlodipine plus terazosin could efficiently decrease blood pressure in model rats,which showed more advantage on blood pressure lowering effects than amlodipine alone or terazosin alone.2) Amlodipine or combined with terazosin may have a potential for alleviating lower urinary tract symptoms(LUTS). Meanwhile,the combination therapy appears to be more suitable for LUTS with predominant irritative symptoms.
3.Efficacy of combined amlodipine and terazosin therapy in male hypertensive patients with lower urinary tract symptoms:a randomized,double-blind clinical trial
[Aims]:Based on the findings in the second part of the study,this trial was to investigate the therapeutic efficacy and safety of amlodipine alone or in combination with terazosin for the presence of hypertension.
[Methods]:A total of 355 patients with Stage 1 or 2 hypertension and LUTS(as defined by an International Prostate Symptom Score of≥10) were randomly assigned to receive 2 mg of terazosin(n=117),5 mg of amlodipine(n=119),or 5 mg of amlodipine plus 2 mg of terazosin(n=119) once daily for a total of 28 days.The primary outcomes were a reduction in the total and subscores of the International Prostate Symptom Score and blood pressure.Analyses were performed by intention to treat.This trial is registered with ClinicalTrials.gov(No.NCT00693199).
[Results]:At day 28 of the trial,the amlodipine plus terazosin group achieved the greatest blood pressure control compared with either the terazosin group(P＜0.01) or amlodipine group(P＜0.05).The amlodipine plus terazosin group also demonstrated comparable efficacy in lowering the total International Prostate Symptom Score and significant improvement in the presence of overactive bladder compared with the terazosin group(P＜0.05) and significant improvement in quality of life compared with the amlodipine group(P＜0.05).All 3 treatment regimens were well tolerated by the study patients.
[Conclusions]:The results of this 4-week,double-blind,randomized trial have demonstrated that in Chinese male hypertensive patients with LUTS,low-dose amlodipine plus terazosin therapy appears to be a safe and effective combination therapy to control both conditions,especially for those with predominant overactive bladder symptoms.
引文
李培军,那彦群,张祥华,et al.2005.高血压对良性前列腺增生细胞增殖与凋亡的影响[J].中华男科学杂志,11:94-97.
潘发明,徐希平2004.高血压的药物基因组学的研究进展[J].国外医学·遗传学分册,27:191-193.
Abrams P,Cardozo L,Fall M,et al.2003.The standardisation of terminology in lower urinary tract function:report from the standardisation sub-committee of the International Continence Society[J].Urology,61:37-49.
Abrams P,Andersson K,Brubaker L,2005.Recommendations of the International Scientific Committee:evaluation and treatment of urinary incontinence,pelvic organ prolapse and faecal incontinence[M],Vol.,Health Publication,Paris.
Abrams P,Andersson KE 2007.Muscarinic receptor antagonists for overactive bladder[J].BJU Int,100:987-1006.
ALLHAT-Collaborative-Research-Group 2000.Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone:the antihypertensive and lipid-lowering treatment to prevent heart attack trial(ALLHAT).ALLHAT Collaborative Research Group[J].JAMA,283:1967-1975.
Andersson K,Appell R,Cardozo L,2005.Pharmacological treatment of urinary incontinence[M],Vol.,Health Publication,Paris.
Arnett DK,Claas SA,Glasser SP 2006.Pharmacogenetics of antihypertensive treatment[J].Vascul Pharmacol,44:107-118.
AUA 2006.Management of BPH clinical guideline.2003.Updated 2006.http://www.auanet.org/guidelines/bph.cfm.
Badawi JK,Langbein S 2006a.Selective beta-adrenoceptor agonists,calcium antagonists and potassium channel openers as a possible medical treatment of the overactive bladder and urge incontinence[J].Pharmazie,61:175-178.
Badawi JK,Li H,Langbein S,et al.2006b.Inhibitory effects of L- and T-type calcium antagonists on contractions of human detrusor muscle[J].Eur J Clin Pharmacol,62:347-354.
Benedict NJ 2007.Sitaxsentan in the management of pulmonary arterial hypertension[J].Am J Health Syst Pharm,64:363-368.
Bengtsson K,Melander O,Orho-Melander M,et al.2001a.Polymorphism in the beta(1)-adrenergic receptor gene and hypertension[J].Circulation,104:187-190.
Bengtsson K,Orho-Melander M,Melander O,et al.2001b.Beta(2)-adrenergic receptor gene variation and hypertension in subjects with type 2 diabetes[J].Hypertension,37:1303-1308.
Bodeker J,Salim SA,Nagel R 1976.Nifedipine(a calcium antagonist) in the treatment of urinary obstruction[J].Dtsch Med Wochenschr,101:1866-1868.
Borjesson M,Magnusson Y,Hjalmarson A,et al.2000.A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure[J].Eur Heart J,21:1853-1858.
Braunwald E,Domanski MJ,Fowler SE,et al.2004.Angiotensin-converting-enzyme inhibition in stable coronary artery disease[J].N Engl J Med,351:2058-2068.
Bray MS,Krushkal J,Li L,et al.2000.Positional genomic analysis identifies the beta(2)-adrenergic receptor gene as a susceptibility locus for human hypertension[J].Circulation,101:2877-2882.
Bristow MR 1993.Changes in myocardial and vascular receptors in heart failure[J].J Am Coll Cardiol,22:61A-71A.
Brodde OE,Michel MC 1999.Adrenergic and muscarinic receptors in the human heart[J].Pharmacol Rev,51:651-690.
Bump R,Steers W,Herschorn S 2006.Duloxetine compared with placebo for the treatment of women with symptoms of bladder overactivity[J].Neurourol Urodyn,25:660-661.
Burgio KL 2004.Current perspectives on management of urgency using bladder and behavioral training[J].J Am Acad Nurse Pract,16:4-7.
Buscher R,Herrmann V,Ring KM,et al.1999.Variability in phenylephrine response and essential hypertension:a search for human alpha(1B)-adrenergic receptor polymorphisms[J].J Pharmacol Exp Ther,291:793-798.
Carbone A,Palleschi G,Conte A,et al.2006.Gabapentin treatment of neurogenic overactive bladder[J].Clin Neuropharmacol,29:206-214.
Chappie CR,Roehrborn CG 2006.A shifted paradigm for the further understanding,evaluation,and treatment of lower urinary tract symptoms in men:focus on the bladder[J].Eur Urol,49:651-658.
Chu FM,Dmochowski R 2006.Pathophysiology of overactive bladder[J].Am J Med,119:3-8.
Cifkova R,Erdine S,Fagard R,et al.2003.Practice guidelines for primary care physicians:2003 ESH/ESC hypertension guidelines[J].J Hypertens,21:1779-1786.
Cockayne DA,Hamilton SG,Zhu QM,et al.2000.Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice[J].Nature,407:1011-1015.
Cohn JN,Tognoni G 2001.A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure[J].N Engl J Med,345:1667-1675.
CUA 2007.Chinese Urological Association Guidelines on Managements of urinary diseases.Available at:http://www.cuan.cn/cnspro/WebDiseaseGuide.aspx.
Dahlof B,Sever PS,Poulter NR,et al.2005.Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required,in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood
Pressure Lowering Arm(ASCOT-BPLA):a multicentre randomised controlled trial[J].Lancet,366:895-906.
Dmochowski RR,Sanders SW,Appell RA,et al.2005.Bladder-health diaries:an assessment of 3-day vs 7-day entries[J].BJU Int,96:1049-1054.
Doulton TW,He FJ,MacGregor GA 2005.Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension[J].Hypertension,45:880-886.
Drysdale CM,McGraw DW,Stack CB,et al.2000.Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness[J].Proc Natl Acad Sci USA,97:10483-10488.
EAU 2004.EAU guidelines on benign prostatic hyperplasia.http://www.uroweb.org/fileadmin/user_upload/Guidelines/BPH.pdf.
Epstein BJ,Gums JG 2005.Can the renin-angiotensin system protect against stroke?A focus on angiotensin Ⅱ receptor blockers[J].Pharmacotherapy,25:531-539.
Feldman RD,Gros R 1998.Impaired vasodilator function in hypertension:the role of alterations in receptor-G protein coupling[J].Trends Cardiovasc Med,8:297-305.
Fossum E,Berge KE,Hoieggen A,et al.2001.Polymorphisms in candidate genes for blood pressure regulation in young men with normal or elevated screening blood pressure[J].Blood Press,10:92-100.
Fournier A,Messerli FH,Achard JM,et al.2004.Cerebroprotection mediated by angiotensin Ⅱ:a hypothesis supported by recent randomized clinical trials[J].J Am Coll Cardiol,43:1343-1347.
Fovaeus M,Andersson KE,Batra S,et al.1987.Effects of calcium,calcium channel blockers and Bay K 8644 on contractions induced by muscarinic receptor stimulation of isolated bladder muscle from rabbit and man[J].J Urol,137:798-803.
Fowler FJ,Jr.,Wennberg JE,Timothy RP,et al.1988.Symptom status and quality of life following prostatectomy[J].JAMA,259:3018-3022.
Fox KM 2003.Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease:randomised,double-blind,placebo-controlled,multicentre trial (the EUROPA study)[J].Lancet,362:782-788.
Fujisawa T,Ikegami H,Yamato E,et al.1997.Trp64Arg mutation of beta3-adrenergic receptor in essential hypertension:insulin resistance and the adrenergic system[J].Am J Hypertens,10:101-105.
Furberg CD,Psaty BM,Meyer JV 1995.Nifedipine.Dose-related increase in mortality in patients with coronary heart disease[J].Circulation,92:1326-1331.
Fuster V,Wayne A,O'Rourke R,2004.Hurst's The Heart[M],Vol.11th edn,McGraw-Hill,New York.
Ganitkevich VY,Isenberg G 1992.Contribution of Ca(2+)-induced Ca2+ release to the[Ca2+]i transients in myocytes from guinea-pig urinary bladder[J].J Physiol,458:119-137.
Gauthier C,Langin D,Balligand JL 2000a.Beta3-adrenoceptors in the cardiovascular system[J].Trends Pharmacol Sci,21:426-431.
Gauthier C,Leblais V,Moniotte S,et al.2000b.The negative inotropic action of catecholamines:role of beta3-adrenoceptors[J].Can J Physiol Pharmacol,78:681-690.
Golomb E,Rosenzweig N,Eilam R,et al.2000.Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats[J].J Androl,21:58-64.
Granneman JG,Lahners KN,Rao DD 1992.Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block[J].Mol Pharmacol,42:964-970.
Gu D,Gupta A,Muntner P,et al.2005.Prevalence of cardiovascular disease risk factor clustering among the adult population of China:results from the International Collaborative Study of Cardiovascular Disease in Asia(InterAsia)[J].Circulation,112:658-665.
Hahntow IN,Koopmans RP,Michel MC 2006.The beta2-adrenoceptor gene and hypertension:is it the promoter or the coding region or neither?[J].J Hypertens,24:1003-1007.
Hannestad YS,Rortveit G,Daltveit AK,et al.2003.Are smoking and other lifestyle factors associated with female urinary incontinence?The Norwegian EPINCONT Study[J].BJOQ 110:247-254.
Hashim H,Malmberg L,Graugaard-Jensen C 2006.Abstracts of the International Continence Society 36th Annual Meeting,Christchurch,New Zealand,27 November-1 December 2006[J].Neurourol Urodyn,25:507-671.
Hashitani H,Bramich NJ,Hirst GD 2000.Mechanisms of excitatory neuromuscular transmission in the guinea-pig urinary bladder[J].J Physiol,524 Pt 2:565-579.
Hawkins GA,Tantisira K,Meyers DA,et al.2006.Sequence,haplotype,and association analysis of ADRbeta2 in a multiethnic asthma case-control study[J].Am J Respir Crit Care Med,174:1101-1109.
Herrmann SM,Nicaud V,Tiret L,et al.2002.Polymorphisms of the beta2-adrenoceptor(ADRB2) gene and essential hypertension:the ECTIM and PEGASE studies[J].J Hypertens,20:229-235.
Herrmann V,Buscher R,Go MM,et al.2000.Beta2-adrenergic receptor polymorphisms at codon 16,cardiovascular phenotypes and essential hypertension in whites and African Americans[J].Am J Hypertens,13:1021-1026.
Homma Y,Kawabe K,Tsukamoto T,et al.1997.Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score[J].Int J Urol,4:40-46.
Huang K,Shi Y,Tang W,et al.2008.No association found between the promoter variants of ADRA1A and schizophrenia in the Chinese population[J].J Psychiatr Res,42:384-388.
Iaccarino G,Lanni F,Cipolletta E,et al.2004.The Glu27 allele of the beta2 adrenergic receptor increases the risk of cardiac hypertrophy in hypertension[J].J Hypertens,22:2117-2122.
Iaccarino G,Izzo R,Trimarco V,et al.2006.Beta2-adrenergic receptor polymorphisms and treatment-induced regression of left ventricular hypertrophy in hypertension[J].Clin Pharmacol Ther,80:633-645.
Jardin A,Bensadoun H,Delauche-Cavallier MC,et al.1994.Long-term treatment of benign prostatic hyperplasia with alfuzosin:a 24-30 month survey.BPHALF Group[J].Br J Urol,74:579-584.
Johnson JA,Terra SG 2002.Beta-adrenergic receptor polymorphisms:cardiovascular disease associations and pharmacogenetics[J].Pharm Res,19:1779-1787.
Jolleys JV,Donovan JL,Nanchahal K,et al.1994.Urinary symptoms in the community:how bothersome are they?[J].Br J Urol,74:551-555.
Joseph MA,Harlow SD,Wei JT,et al.2003.Risk factors for lower urinary tract symptoms in a population-based sample of African-American men[J].Am J Epidemiol,157:906-914.
Julius S,Kjeldsen SE,Weber M,et al.2004.Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine:the VALUE randomised trial[J].Lancet,363:2022-2031.
Julius S,Weber MA,Kjeldsen SE,et al.2006.The Valsartan Antihypertensive Long-Term Use Evaluation(VALUE) trial:outcomes in patients receiving mono therapy[J].Hypertension,48:385-391.
Kajioka S,Nakayama S,McMurray G,et al.2002.Ca(2+) channel properties in smooth muscle cells of the urinary bladder from pig and human[J].Eur J Pharmacol,443:19-29.
Kaplan SA,Bowers DL,Te AE,et al.1996.Differential diagnosis of prostatism:A 12-year retrospective analysis of symptoms,urodynamics and satisfaction with therapy[J].J Urol,155:1305-1308.
Kaplan SA,Roehrborn CG,Rovner ES,et al.2006.Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder:a randomized controlled trial[J].JAMA,296:2319-2328.
Kirstein SL,Insel PA 2004.Autonomic nervous system pharmacogenomics:a progress report[J].Pharmacol Rev,56:31-52.
Kjeldsen SE,Julius S,Mancia G,et al.2006.Effects of valsartan compared to amlodipine on preventing type 2 diabetes in high-risk hypertensive patients:the VALUE trial[J].J Hypertens,24:1405-1412.
Knutson T,Pettersson S,Dahlstrand C 2001.Pressure-flow studies for patient selection in the treatment of symptomatic BPH-a one-year follow-up study[J].Scand J Urol Nephrol,35:470-475.
Krum H,Gilbert RE 2007.Novel therapies blocking the renin-angiotensin-aldosterone system in the management of hypertension and related disorders[J].J Hypertens,25:25-35.
Lee JY,Kim HW,Lee SJ,et al.2004.Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder[J].BJU Int,94:817-820.
Leenen FH,Nwachuku CE,Black HR,et al.2006.Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial[J].Hypertension,48:374-384.
Lei B,Morris DP,Smith MP,et al.2005.Novel human alphala-adrenoceptor single nucleotide polymorphisms alter receptor pharmacology and biological function[J].Naunyn Schmiedebergs Arch Pharmacol,371:229-239.
Lelias JM,Kaghad M,Rodriguez M,et al.1993.Molecular cloning of a human beta 3-adrenergic receptor cDNA[J].FEBS Lett,324:127-130.
Levin R,Chichester P,Hass M,et al.2002.Obstructive bladder dysfunction:morphological, biochemical and molecular changes[J].Eur Urol Suppl,1:14-20.
Liggett SB,Wagoner LE,Craft LL,et al.1998.The Ilel64 beta2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure[J].J Clin Invest,102:1534-1539.
Liggett SB 2000a.The pharmacogenetics of beta2-adrenergic receptors:relevance to asthma[J].J Allergy Clin Immunol,105:S487-492.
Liggett SB 2000b.beta(2)-adrenergic receptor pharmacogenetics[J].Am J Respir Crit Care Med,161:S197-201.
Lima JJ,Holbrook JT,Wang J,et al.2006.The C523A beta2 adrenergic receptor polymorphism associates with markers of asthma severity in African Americans[J].J Asthma,43:185-191.
Liu L,Zhang Y,Liu G,et al.2005.The Felodipine Event Reduction(FEVER) Study:a randomized long-term placebo-controlled trial in Chinese hypertensive patients[J].J Hypertens,23:2157-2172.
MacKinnon M,Shurraw S,Akbari A,et al.2006.Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease:a systematic review of the efficacy and safety data[J].Am J Kidney Dis,48:8-20.
MacMahon S 1990.Antihypertensive drug treatment:the potential,expected and observed effects on vascular disease[J].J Hypertens Suppl,8:S239-244.
Maggi CA,Giuliani S,Patacchini R,et al.1989.Multiple sources of calcium for contraction of the human urinary bladder muscle[J].Br J Pharmacol,98:1021-1031.
Malacco E,Vari N,Capuano V,et al.2003.A randomized,double-blind,active-controlled,parallel-group comparison of valsartan and amlodipine in the treatment of isolated systolic hypertension in elderly patients:the Val-Syst study[J].Clin Ther,25:2765-2780.
Marinese D,Patel R,Walden PD 2003.Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice[J].Prostate,54:230-237.
Maruenda J,Bhatnagar V,Lowenthal DT 1999.Hypertension in the elderly with coexisting benign prostatic hyperplasia[J].Urology,53:7-12;discussion 12-13,41-12.
Masaki T 1995.Possible role of endothelin in endothelial regulation of vascular tone[J].Annu Rev Pharmacol Toxicol,35:235-255.
Mason RP,Marche P,Hintze TH 2003.Novel vascular biology of third-generation L-type calcium channel antagonists:ancillary actions of amlodipine[J].Arterioscler Thromb Vasc Biol,23:2155-2163.
Matityahou A,Rosenzweig N,Golomb E 2003.Rapid proliferation of prostatic epithelial cells in spontaneously hypertensive rats:a model of spontaneous hypertension and prostate hyperplasia[J].J Androl,24:263-269.
McCaffery JM,Pogue-Geile MF,Ferrell RE,et al.2002.Variability within alpha-and beta-adrenoreceptor genes as a predictor of cardiovascular function at rest and in response to mental challenge[J].J Hypertens,20:1105-1114.
McCall KL,Craddock D,Edwards K 2006.Effect of angiotensin-converting enzyme inhibitors and angiotensin Ⅱ type 1 receptor blockers on the rate of new-onset diabetes mellitus:a review and pooled analysis[J].Pharmacotherapy,26:1297-1306.
McKelvie RS,Yusuf S,Pericak D,et al.1999.Comparison of candesartan,enalapril,and their combination in congestive heart failure:randomized evaluation of strategies for left ventricular dysfunction(RESOLVD) pilot study.The RESOLVD Pilot Study Investigators[J].Circulation,100:1056-1064.
McMurray JJ,Ostergren J,Swedberg K,et al.2003.Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors:the CHARM-Added trial[J].Lancet,362:767-771.
McVary KT 2006.BPH:epidemiology and comorbidities[J].Am J Manag Care,12:S122-128.
Messerli FH 2002.Vasodilatory edema:a common side effect of antihypertensive therapy[J].Curr Cardiol Rep,4:479-482.
Messerli FH,Weir MR,Neutel JM 2002.Combination therapy of amlodipine/benazepril versus monotherapy of amlodipine in a practice-based setting[J].Am J Hypertens,15:550-556.
Michel MC,Heemann U,Schumacher H,et al.2004.Association of hypertension with symptoms of benign prostatic hyperplasia[J].J Urol,172:1390-1393.
Milsom I,Abrams P,Cardozo L,et al.2001.How widespread are the symptoms of an overactive bladder and how are they managed?A population-based prevalence study[J].BJU Int,87:760-766.
Mochtar CA,Laan W,Van Houwelingen KP,et al.2006.Polymorphisms in the alpha1A-adrenoceptor gene do not modify the short-and long-term efficacy of alpha1-adrenoceptor antagonists in the treatment of benign prostatic hyperplasia[J].BJU Int,97:852-855.
Moore JD,Mason DA,Green SA,et al.1999.Racial differences in the frequencies of cardiac beta(1)-adrenergic receptor polymorphisms:analysis of c145A＞G and c1165G＞C[J].Hum Mutat,14:271.
Moorthy P,Lapitan MC,Quek PL,et al.2004.Prevalence of overactive bladder in Asian men:an epidemiological survey[J].BJU Int,93:528-531.
Moosmang S,Lenhardt P,Haider N,et al.2005.Mouse models to study L-type calcium channel function[J].Pharmacol Ther,106:347-355.
Nalbantgil S,Nalbantgil I,Onder R 2000.Clinically additive effect between doxazosin and amlodipine in the treatment of essential hypertension[J].Am J Hypertens,13:921-926.
NCBI dbSNP database[J].
Nicolas Torralba JA,Tornero Ruiz J,Banon Perez V,et al.2003.Relation between hypertension and clinical cases of benign prostatic hyperplasia[J].Arch Esp Urol,56:355-358.
NIH Management of hypertension in adults in primary care:partial update.The National Institute for Health and Clinical Excellence[online][J].Available from URL:http://www.nice.org.uk/guidance/CG34.
Nissen SE,Tuzcu EM,Libby P,et al.2004a.Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure:the CAMELOT study:a randomized controlled trial[J].JAMA,292:2217-2225.
Nissen SE,Tuzcu EM,Schoenhagen P,et al.2004b.Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis:a randomized controlled trial[J].JAMA,291:1071-1080.
Nonen S,Okamoto H,Fujio Y,et al.2008.Polymorphisms of norepinephrine transporter and adrenergic receptor alpha ID are associated with the response to beta-blockers in dilated cardiomyopathy[J].Pharmacogenomics J,8:78-84.
Nowara A,Witek A,Wilk K 2007.[Diagnostic and treatment of overactive bladder][J].Ginekol Pol,78:549-553.
O'Sullivan M,Murphy C,Deasy C,et al.2004.Effects of transurethral resection of prostate on the quality of life of patients with benign prostatic hyperplasia[J].J Am Coll Surg,198:394-403.
Ouslander JG 2004.Management of overactive bladder[J].N Engl J Med,350:786-799.
Parsons JK 2007.Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms:new approaches to old problems[J].J Urol,178:395-401.
Peters TJ,Donovan JL,Kay HE,et al.1997.The International Continence Society“Benign Prostatic Hyperplasia”Study:the botherosomeness of urinary symptoms[J].J Urol,157:885-889.
Pinggera GM,Mitterberger M,Steiner E,et al.2008.Association of lower urinary tract symptoms and chronic ischaemia of the lower urinary tract in elderly women and men:assessment using colour Doppler ultrasonography[J].BJU Int,102:470-474.
Podlowski S,Wenzel K,Luther HP,et al.2000.Betal-adrenoceptor gene variations:a role in idiopathic dilated cardiomyopathy?[J].J Mol Med,78:87-93.
Poldermans D,Gamboa R,Fomina I 2006.Comparative safety and blood pressure-lowering efficacy of a combination of amlodipine/valsartan and lisinopril/HCTZ in patients with stage 2 hypertension[abstract P-217].Presented at American Society of Hypertension;New York (NY);[J].
Pool JL 1991.Combination antihypertensive therapy with terazosin and other antihypertensive agents:results of clinical trials[J].Am Heart J,122:926-931.
Pool JL,Schmieder RE,Azizi M,et al.2007.Aliskiren,an orally effective renin inhibitor,provides antihypertensive efficacy alone and in combination with valsartan[J].Am J Hypertens,20:11-20.
Poole-Wilson PA,Lubsen J,Kirwan BA,et al.2004.Effect of long-acting nifedipine on
mortality and cardiovascular morbidity in patients with stable angina requiring treatment(ACTION trial):randomised controlled trial[J].Lancet,364:849-857.
Port JD,Bristow MR 2001.Altered beta-adrenergic receptor gene regulation and signaling in chronic heart failure[J].J Mol Cell Cardiol,33:887-905.
Poulter NR,Wedel H,Dahlof B,et al.2005.Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes
Trial-Blood Pressure Lowering Arm(ASCOT-BPLA)[J].Lancet,366:907-913.
Psaty BM,Smith NL,Siscovick DS,et al.1997.Health outcomes associated with antihypertensive therapies used as first-line agents.A systematic review and meta-analysis[J].JAMA,277:739-745.
Rocha R,Williams GH 2002.Rationale for the use of aldosterone antagonists in congestive heart failure[J].Drugs,62:723-731.
Rohrmann S,Smit E,Giovannucci E,et al.2005.Association between markers of the metabolic syndrome and lower urinary tract symptoms in the Third National Health and Nutrition Examination Survey(NHANES III)[J].Int J Obes(Lond),29:310-316.
Rosen R,Altwein J,Boyle P,et al.2003.Lower urinary tract symptoms and male sexual dysfunction:the multinational survey of the aging male(MSAM-7)[J].Eur Urol,44:637-649.
Rosmond R,Ukkola O,Chagnon M,et al.2000.Polymorphisms of the beta2-adrenergic receptor gene(ADRB2) in relation to cardiovascular risk factors in men[J].J Intern Med,248:239-244.
Rud T,Andersson KE,Ulmsten U 1979.Effects of nifedipine in women with unstable bladders[J].Urol Int,34:421-429.
Rudolph AE,Rocha R,McMahon EG 2004.Aldosterone target organ protection by eplerenone[J].Mol Cell Endocrinol,217:229-238.
Schelleman H,Klungel OH,van Duijn CM,et al.2006.Drug-gene interaction between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and antihypertensive therapy[J],Ann Pharmacother,40:212-218.
Sehti A,Tybjaerg-Hansen A,Jensen G,et al.2005.164Ile allele in the(32-adrenergic receptor gene is associated with risk of elevated blood pressure in women.The Copenhagen City Heart Study.[J].Pharmacogenet Genom,15:633-645.
Sellers DJ,McKay N 2007.Developments in the pharmacotherapy of the overactive bladder[J].Curr Opin Urol,17:223-230.
Shioji K,Kokubo Y,Mannami T,et al.2004.Association between hypertension and the alpha-adducin,betal-adrenoreceptor,and G-protein beta3 subunit genes in the Japanese population;the Suita study[J].Hypertens Res,27:31-37.
Sica DA 2002.Rationale for fixed-dose combinations in the treatment of hypertension:the cycle repeats[J].Drugs,62:443-462.
Sica DA 2003.Combination angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy:its role in clinical practice[J].J Clin Hypertens(Greenwich),5:414-420.
Small KM,Wagoner LE,Levin AM,et al.2002.Synergistic polymorphisms of betal-and alpha2C-adrenergic receptors and the risk of congestive heart failure[J].N Engl J Med,347:1135-1142.
Snapir A,Heinonen P,Tuomainen TP,et al.2001.An insertion/deletion polymorphism in the alpha2B-adrenergic receptor gene is a novel genetic risk factor for acute coronary events[J].J Am Coll Cardiol,37:1516-1522.
Snapir A,Koskenvuo J,Toikka J,et al.2003a.Effects of common polymorphisms in the alpha 1A-,alpha2B-,betal-and beta2-adrenoreceptors on haemodynamic responses to adrenaline[J].Clin Sci(Lond),104:509-520.
Snapir A,Scheinin M,Groop LC,et al.2003b.The insertion/deletion variation in the alpha2B-adrenoceptor does not seem to modify the risk for acute myocardial infarction,but may modify the risk for hypertension in sib-pairs from families with type 2 diabetes[J].Cardiovasc Diabetol,2:15.
Sofowora GG,Dishy V,Landau R,et al.2004.Alpha 1A-adrenergic receptor polymorphism and vascular response[J].Clin Pharmacol Ther,75:539-545.
Srikrishna S,Robinson D,Cardozo L,et al.2007.Management of overactive bladder syndrome[J].Postgrad Med J,83:481-486.
Staessen JA,Li Y,Richart T 2006.Oral renin inhibitors[J].Lancet,368:1449-1456.
Stergiou GS,Makris T,Papavasiliou M,et al.2005.Comparison of antihypertensive effects of an angiotensin-converting enzyme inhibitor,a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocker monotherapy[J].J Hypertens,23:883-889.
Stewart WF,Van Rooyen JB,Cundiff GW,et al.2003.Prevalence and burden of overactive bladder in the United States[J].World J Urol,20:327-336.
Strazzullo P,lacone R,Siani A,et al.2001.Relationship of the Trp64Arg polymorphism of the beta3-adrenoceptor gene to central adiposity and high blood pressure:interaction with age.Cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study[J].J Hypertens,19:399-406.
Sugaya K,Kadekawa K,Ikehara A,et al.2003.Influence of hypertension on lower urinary tract symptoms in benign prostatic hyperplasia[J].Int J Urol,10:569-574;discussion 575.
Swithinbank L,Hashim H,Abrams P 2005.The effect of fluid intake on urinary symptoms in women[J].J Urol,174:187-189.
Taylor JA,Hand GA,Johnson DG,et al.1992.Augmented forearm vasoconstriction during dynamic exercise in healthy older men[J].Circulation,86:1789-1799.
Taylor M,Bristow M 2004a.The emerging pharmacogenomics of the betaadrenergic receptors[J].Congest Heart Fail,10:281-288.
Taylor MR,Bristow MR 2004b.The emerging pharmacogenomics of the beta-adrenergic receptors[J].Congest Heart Fail,10:281-288.
Teramoto N,Yunoki T,Ikawa S,et al.2001.The involvement of L-type Ca(2+) channels in the relaxant effects of the ATP-sensitive K(+) channel opener ZD6169 on pig urethral smooth muscle[J].Br J Pharmacol,134:1505-1515.
Tesson F,Charron P,Peuchmaurd M,et al.1999.Characterization of a unique genetic variant in the beta 1-adrenoceptor gene and evaluation of its role in idiopathic dilated cardiomyopathy.CARDIGENE Group[J].J Mol Cell Cardiol,31:1025-1032.
Tonolo G,Melis MG,Secchi G,et al.1999.Association of Trp64Arg beta 3-adrenergic-receptor gene polymorphism with essential hypertension in the Sardinian population[J].J Hypertens,17:33-38.
Trotta R,Donati MB,Iacoviello L 2004.Trends in pharmacogenomics of drugs acting on hypertension[J].Pharmacol Res,49:351-356.
Turnbull F 2003.Effects of different blood-pressure-lowering regimens on major cardiovascular events:results of prospectively-designed overviews of randomised trials[J].Lancet,362:1527-1535.
Turner ST,Schwartz GL 2005.Gene markers and antihypertensive therapy[J].Curr Hypertens Rep,7:21-30.
Unwala DJ,Barboglio P,Gousse AE 2007.Repeated botulinum toxin injection for idiopathic overactive bladder:will chemodenervation become a long-term solution?[J].Curr Urol Rep,8:419-424.
van Spronsen A,Nahmias C,Krief S,et al.1993.The promoter and intron/exon structure of the human and mouse beta 3-adrenergic-receptor genes[J].Eur J Biochem,213:1117-1124.
Vendrell J,Gutierrez C,Broch M,et al.1998.Beta 3-adrenoreceptor gene polymorphism and leptin.Lack of relationship in type 2 diabetic patients[J].Clin Endocrinol(Oxf),49:679-683.
Von Wowern F,Bengtsson K,Lindblad U,et al.2004.Functional variant in the(alpha)2B adrenoceptor gene,a positional candidate on chromosome 2,associates with hypertension[J].Hypertension,43:592-597.
Weber MA,Julius S,Kjeldsen SE,et al.2004.Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial[J].Lancet,363:2049-2051.
Wegener JW,Schulla V,Lee TS,et al.2004.An essential role of Cav1.2 L-type calcium channel for urinary bladder function[J].FASEB J,18:1159-1161.
Weiser M,Frishman WH,Michaelson MD,et al.1997.The pharmacologic approach to the treatment of obesity[J].J Clin Pharmacol,37:453-473.
Whelton PK,Barzilay J,Cushman WC,et al.2005.Clinical outcomes in antihypertensive treatment of type 2 diabetes,impaired fasting glucose concentration,and normoglycemia:Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial(ALLHAT)[J].Arch Intern Med,165:1401-1409.
Whitworth JA 2003.2003 World Health Organization(WHO)/International Society of Hypertension(ISH) statement on management of hypertension[J].J Hypertens,21:1983-1992.
WHO,2002.Reducing Risks,Promoting Life[M],Vol.,World Health Organization,Geneva,Switzerland.
Wong SY,Woo J,Hong A,et al.2006.Risk factors for lower urinary tract symptoms in southern Chinese men[J].Urology,68:1009-1014.
Wu C,Sui G,Fry CH 2002.The role of the L-type Ca(2+) channel in refilling functional intracellular Ca(2+) stores in guinea-pig detrusor smooth muscle[J].J Physiol,538:357-369.
Wu H,Tang W,Li H,et al.2006.Association of the beta2-adrenergic receptor gene with essential hypertension in the non-Han Chinese Yi minority human population[J].J Hypertens,24:1041-1047.
Xie HG,Stein CM,Kim RB,et al.1999.Frequency of functionally important beta-2 adrenoceptor polymorphisms varies markedly among African-American,Caucasian and Chinese individuals[J].Pharmacogenetics,9:511-516.
Yamada K,Ishiyama-Shigemoto S,Ichikawa F,et al.1999.Polymorphism in the 5'-leader cistron of the beta2-adrenergic receptor gene associated with obesity and type 2 diabetes[J].J Clin Endocrinol Metab,84:1754-1757.
Yanagisawa M,Kurihara H,Kimura S,et al.1988.A novel potent vasoconstrictor peptide produced by vascular endothelial cells[J].Nature,332:411-415.
Yusuf S,Sleight P,Pogue J,et al.2000.Effects of an angiotensin-converting-enzyme inhibitor,ramipril,on cardiovascular events in high-risk patients.The Heart Outcomes Prevention Evaluation Study Investigators[J].N Engl J Med,342:145-153.
Zanchetti A,Rosei EA,Dal Palu C,et al.1998.The Verapamil in Hypertension and Atherosclerosis Study(VHAS):results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness[J].J Hypertens,16:1667-1676.
Zanchetti A,Bond MG,Hennig M,et al.2002.Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis:principal results of the European Lacidipine Study on Atherosclerosis(ELSA),a randomized,double-blind,long-term trial[J].Circulation,106:2422-2427.
Zhang H,Li X,Huang J,et al.2005.Cardiovascular and metabolic phenotypes in relation to the ADRA2B insertion/deletion polymorphism in a Chinese population[J].J Hypertens,23:2201-2207.
Zillich AJ,Garg J,Basu S,et al.2006.Thiazide diuretics,potassium,and the development of diabetes:a quantitative review[J].Hypertension,48:219-224.
Banzet O,Colin JN,Thibonnier M,et al.1983.Acute antihypertensive effect and pharmacokinetics of a tablet preparation of nifedipine[J].Eur J Clin Pharmacol,24:145-150.
Benetos A,Cambien F,Gautier S,et al.1996.Influence of the angiotensin Ⅱ type 1 receptor gene polymorphism on the effects of perindopril and nitrendipine on arterial stiffness in hypertensive individuals[J].Hypertension,28:1081-1084.
Brown MJ,Palmer CR,Castaigne A,et al.2000.Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study:Intervention as a Goal in Hypertension Treatment (INSIGHT)[J].Lancet,356:366-372.
Chung M,Reitberg D,Gaffney M,et al.1987.Clinical pharmacokinetics of nifedipine gastrointestinal therapeutic system.A controlled-release formulation of nifedipine[J].Am J Med,83:10-14.
Cockcroft JR,Gazis AG,Cross DJ,et al.2000.Beta(2)-adrenoceptor polymorphism determines vascular reactivity in humans[J].Hypertension,36:371-375.
Dishy V,Sofowora GG,Xie HG,et al.2001.The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization[J].N Engl J Med,345:1030-1035.
Dudley C,Keavney B,Casadei B,et al.1996.Prediction of patient responses to antihypertensive drugs using genetic polymorphisms:investigation of renin-angiotensin system genes[J].J Hypertens,14:259-262.
Eckert RE,Karsten AJ,Utz J,et al.2000.Regulation of renal artery smooth muscle tone by alphal-adrenoceptors:role of voltage-gated calcium channels and intracellular calcium stores[J].Urol Res,28:122-127.
Eichler HG,Blaschke TF,Hoffman BB 1990.Decreased responsiveness of superficial hand veins to phenylephrine in black normotensive males[J].J Cardiovasc Pharmacol,16:177-181.
Garovic VD,Joyner MJ,Dietz NM,et al.2003.Beta(2)-adrenergic receptor polymorphism and nitric oxide-dependent forearm blood flow responses to isoproterenol in humans[J].J Physiol,546:583-589.
Gratze G,Fortin J,Labugger R,et al.1999.beta-2 Adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians[J].Hypertension,33:1425-1430.
Green SA,Turki J,Innis M,et al.1994.Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties[J].Biochemistry, 33:9414-9419.
Han C,Abel PW,Minneman KP 1987.Alpha 1-adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle[J].Nature,329:333-335.
Han C,Li J,Minneman KP 1990.Subtypes of alpha 1-adrenoceptors in rat blood vessels[J].Eur J Pharmacol,190:97-104.
Hingorani AD,Jia H,Stevens PA,et al.1995.Renin-angiotensin system gene polymorphisms influence blood pressure and the response to angiotensin converting enzyme inhibition[J].J Hypertens,13:1602-1609.
Hoit BD,Suresh DP,Craft L,et al.2000.beta2-adrenergic receptor polymorphisms at amino acid 16 differentially influence agonist-stimulated blood pressure and peripheral blood flow in normal individuals[J].Am Heart J,139:537-542.
Krakoff LR 1993.Effectiveness of nifedipine gastrointestinal therapeutic system for treatment of hypertension:results of the MATH Trial[J].J Cardiovasc Pharmacol,21 Suppl 2:S14-17.
Liljedahl U,Karlsson J,Melhus H,et al.2003.A microarray minisequencing system for pharmacogenetic profiling of antihypertensive drug response[J].Pharmacogenetics,13:7-17.
Moffett S,Mouillac B,Bonin H,et al.1993.Altered phosphorylation and desensitization patterns of a human beta 2-adrenergic receptor lacking the palmitoylated Cys341[J].EMBO J,12:349-356.
Nair R,Dyer DC 1996.Pharmacological characterization of alpha 1-adrenoceptors in porcine uterine artery[J].Eur J Pharmacol,312:45-51.
O'Dowd BF,Hnatowich M,Regan JW,et al.1988.Site-directed mutagenesis of the cytoplasmic domains of the human beta 2-adrenergic receptor.Localization of regions involved in G protein-receptor coupling[J].J Biol Chem,263:15985-15992.
Psaty BM,Smith NL,Heckbert SR,et al.2002.Diuretic therapy,the alpha-adducin gene variant,and the risk of myocardial infarction or stroke in persons with treated hypertension[J].JAMA,287:1680-1689.
Rokosh DG,Simpson PC 2002.Knockout of the alpha 1A/C-adrenergic receptor subtype:the alpha 1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure[J].Proc Natl Acad Sci U S A,99:9474-9479.
Rudner XL,Berkowitz DE,Booth JV,et al.1999.Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age[J].Circulation,100:2336-2343.
Shibata K,Hirasawa A,Moriyama N,et al.1996.Alpha 1a-adrenoceptor polymorphism:pharmacological characterization and association with benign prostatic hypertrophy[J].Br J Pharmacol,118:1403-1408.
Sofowora GG,Dishy V,Landau R,et al.2004.Alpha 1A-adrenergic receptor polymorphism and vascular response[J].Clin Pharmacol Ther,75:539-545.
Soons PA,Schoemaker HC,Cohen AF,et al.1992.Intraindividual variability in nifedipine pharmacokinetics and effects in healthy subjects[J].J Clin Pharmacol,32:324-331.
Stein CM,Lang CC,Singh I,et al.2000.Increased vascular adrenergic vasoconstriction and decreased vasodilation in blacks.Additive mechanisms leading to enhanced vascular reactivity[J].Hypertension,36:945-951.
Taburet AM,Singlas E,Colin JN,et al.1983.Pharmacokinetic studies of nifedipine tablet.Correlation with antihypertensive effects[J].Hypertension,5:1129-33.
Testa R,Guarneri L,Taddei C,et al.1996.Functional antagonistic activity of Rec 15/2739,a novel alpha-1 antagonist selective for the lower urinary tract,on noradrenaline-induced contraction of human prostate and mesenteric artery[J].J Pharmacol Exp Ther,277:1237-1246.
Turner ST,Chapman AB,Schwartz GL,et al.2003.Effects of endothelial nitric oxide synthase,alpha-adducin,and other candidate gene polymorphisms on blood pressure response to hydrochlorothiazide[J].Am J Hypertens,16:834-839.
Villalobos-Molina R,Lopez-Guerrero JJ,Ibarra M 1997.Alpha ID-and alpha 1 A-adrenoceptors mediate contraction in rat renal artery[J].Eur J Pharmacol,322:225-227.
Xie HG,Kim RB,Stein CM,et al.1999.AlphalA-adrenergic receptor polymorphism:association with ethnicity but not essential hypertension[J].Pharmacogenetics,9:651-656
Badawi JK,Li H,Langbein S,et al.2006.Inhibitory effects of L-and T-type calcium antagonists on contractions of human detrusor muscle[J].Eur J Clin Pharmacol,62:347-354.
Bouchelouche K,Andersen L,Alvarez S,et al.2005.Increased contractile response to phenylephrine in detrusor of patients with bladder outlet obstruction:effect of the alpha1A and alpha1D-adrenergic receptor antagonist tamsulosin[J].J Urol,173:657-661.
Chappie CR,Roehrborn CG 2006.A shifted paradigm for the further understanding,evaluation,and treatment of lower urinary tract symptoms in men:focus on the bladder[J].Eur Urol,49:651-658.
Cifkova R,Erdine S,Fagard R,et al.2003.Practice guidelines for primary care physicians:2003 ESH/ESC hypertension guidelines[J].J Hypertens,21:1779-1786.
Das AK,Leggett RE,Whitbeck C,et al.2002.Effect of doxazosin on rat urinary bladder function after partial outlet obstruction[J].Neurourol Urodyn,21:160-166.
Fovaeus M,Andersson KE,Batra S,et al.1987.Effects of calcium,calcium channel blockers and Bay K 8644 on contractions induced by muscarinic receptor stimulation of isolated bladder muscle from rabbit and man[J].J Urol,137:798-803.
Ganitkevich VY,Isenberg G 1992.Contribution of Ca(2+)-induced Ca2+ release to the[Ca2+]i transients in myocytes from guinea-pig urinary bladder[J].J Physiol,458:119-137.
Goepel M,Wittmann A,Rubben H,et al.1997.Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate[J].Urol Res,25:199-206.
Hashitani H,Bramich NJ,Hirst GD 2000.Mechanisms of excitatory neuromuscular transmission in the guinea-pig urinary bladder[J].J Physiol,524 Pt 2:565-579.
Irwin DE,Milsom I,Hunskaar S,et al.2006.Population-based survey of urinary incontinence,overactive bladder,and other lower urinary tract symptoms in five countries:results of the EPIC study[J].Eur Urol,50:1306-1314;discussion 1314-1305.
Joseph MA,Harlow SD,Wei JT,et al.2003.Risk factors for lower urinary tract symptoms in a population-based sample of African-American men[J].Am J Epidemiol,157:906-914.
Kaplan SA,Roehrborn CG,Rovner ES,et al.2006.Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder:a randomized controlled trial[J].JAMA,296:2319-2328.
Lee JY,Kim HW,Lee SJ,et al.2004.Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder[J].BJU Int,94:817-820.
Levin R,Chichester P,Hass M,et al.2002.Obstructive bladder dysfunction:morphological, biochemical and molecular changes[J].Eur Urol Suppl,1:14-20.
Malmgren A,Sjogren C,Uvelius B,et al.1987.Cystometrical evaluation of bladder instability in rats with infravesical outflow obstruction[J].J Urol,137:1291-1294.
Nalbantgil S,Nalbantgil I,Onder R 2000.Clinically additive effect between doxazosin and amlodipine in the treatment of essential hypertension[J].Am J Hypertens,13:921-926.
NIH Management of hypertension in adults in primary care:partial update.The National Institute for Health and Clinical Excellence[online][J].Available from URL:http://www.nice.org.uk/guidance/CG34.
Nomiya M,Yamaguchi O 2003.A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders[J].J Urol,170:649-653.
Ozturk H,Onen A,Guneli E,et al.2003.Effects of methoctramine on bladder overactivity in a rat model[J].Urology,61:671-676.
Pandita RK,Persson K,Hedlund P,et al.1998.Testosterone-induced prostatic growth in the rat causes bladder overactivity unrelated to detrusor hypertrophy[J].Prostate,35:102-108.
Parsons JK 2007.Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms:new approaches to old problems[J].J Urol,178:395-401.
Pinggera GM,Mitterberger M,Pallwein L,et al.2008a.alpha-Blockers improve chronic ischaemia of the lower urinary tract in patients with lower urinary tract symptoms[J].BJU Int,101:319-324.
Pinggera GM,Mitterberger M,Steiner E,et al.2008b.Association of lower urinary tract symptoms and chronic ischaemia of the lower urinary tract in elderly women and men:assessment using colour Doppler ultrasonography[J].BJU Int,102:470-474.
Pool JL 1991.Combination antihypertensive therapy with terazosin and other antihypertensive agents:results of clinical trials[J].Am Heart J,122:926-931.
Pressler L,Santarosa R,Te A,et al.1997.The incidence of hypertension(HTN) in a population of men with benign prostatic hyperplasia(BPH):analysis based on the AUA symptom score and race[J].Urology,147(Suppl):371.
Rohrmann S,Smit E,Giovannucci E,et al.2005.Association between markers of the metabolic syndrome and lower urinary tract symptoms in the Third National Health and Nutrition Examination Survey(NHANES III)[J].Int J Obes(Lond),29:310-316.
Rosen R,Altwein J,Boyle P,et al.2003.Lower urinary tract symptoms and male sexual dysfunction:the multinational survey of the aging male(MSAM-7)[J].Eur Urol,44:637-649.
Rud T,Andersson KE,Ulmsten U 1979.Effects of nifedipine in women with unstable bladders[J]. Urol Int,34:421-429.
Sica DA 2002.Rationale for fixed-dose combinations in the treatment of hypertension:the cycle repeats[J].Drugs,62:443-462.
Smith MS,Schambra UB,Wilson KH,et al.1999.Alpha 1-adrenergic receptors in human spinal cord:specific localized expression of mRNA encoding alpha 1-adrenergic receptor subtypes at four distinct levels[J].Brain Res Mol Brain Res,63:254-261.
Sugaya K,Nishijima S,Miyazato M,et al.2002.Effects of intrathecal injection of tamsulosin and
naftopidil,alpha-1A and-1D adrenergic receptor antagonists,on bladder activity in rats[J].Neurosci Lett,328:74-76.
Tatemichi S,Akiyama K,Kobayashi M,et al.2006.A selective alpha1A-adrenoceptor antagonist inhibits detrusor overactivity in a rat model of benign prostatic hyperplasia[J].J Urol,176:1236-1241.
Taylor JA,Hand GA,Johnson DG,et al.1992.Augmented forearm vasoconstriction during dynamic exercise in healthy older men[J].Circulation,86:1789-1799.
Teramoto N,Yunoki T,Ikawa S,et al.2001.The involvement of L-type Ca(2+) channels in the relaxant effects of the ATP-sensitive K(+) channel opener ZD6169 on pig urethral smooth muscle[J].Br J Pharmacol,134:1505-1515.
Wegener JW,Schulla V,Lee TS,et al.2004.An essential role of Cav1.2 L-type calcium channel for urinary bladder function[J].FASEB J,18:1159-1161.
Whitworth JA 2003.2003 World Health Organization(WHO)/International Society of Hypertension(ISH) statement on management of hypertension[J].J Hypertens,21:1983-1992.
Wong SY,Woo J,Hong A,et al.2006.Risk factors for lower urinary tract symptoms in southern Chinese men[J].Urology,68:1009-1014.
Wu C,Sui G,Fry CH 2002.The role of the L-type Ca(2+) channel in refilling functional intracellular Ca(2+) stores in guinea-pig detrusor smooth muscle[J].J Physiol,538:357-369.
Yang Y,Zhao XF,Li HZ,et al.2007.Efficacy and safety of combined therapy with terazosin and tolteradine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia:a prospective study[J].Chin Med J(Engl),120:370-374.
Achari R,Hosmane B,Bonacci E,et al.2000.The relationship between terazosin dose and blood pressure response in hypertensive patients[J].J Clin Pharmacol,40:1166-1172.
Anderson KE 1993.Pharmacology of lower urinary tract smooth muscles and penile erectile tissues[J].Pharmacol Rev,45:253-308.
Aso Y,Homma Y 1995.Clinical research criteria:response criteria for evaluating efficacy of treatments for benign prostatic hypertrophy[J].Br J Urol,76 Suppl 1:69-73.
AUA 2006.Management of BPH clinical guideline.2003.Updated 2006.http://www.auanet.org/guidelines/bph.cfm.
Badawi JK,Li H,Langbein S,et al.2006.Inhibitory effects of L-and T-type calcium antagonists on contractions of human detrusor muscle[J].Eur J Clin Pharmacol,62:347-354.
Chappie CR,Roehrborn CG 2006.A shifted paradigm for the further understanding,evaluation,and treatment of lower urinary tract symptoms in men:focus on the bladder[J].Eur Urol,49:651-658.
Chobanian AV,Bakris GL,Black HR,et al.2003.Seventh report of the Joint National Committee on Prevention,Detection,Evaluation,and Treatment of High Blood Pressure[J].Hypertension,42:1206-1252.
CUA 2007.Chinese Urological Association Guidelines on Managements of urinary diseases.Available at:http://www.cuan.cn/cnspro/WebDiseaseGuide.aspx.
EAU 2004.EAU guidelines on benign prostatic hyperplasia.http://www.uroweb.org/fileadmin/user_upload/Guidelines/BPH.pdf.
Eckert RE,Schreier U,Drescher P,et al.1995.Regulation of prostatic smooth muscle contractility by intracellular second messengers:implications for the conservative treatment of benign prostatic hyperplasia[J].Urol Int,54:6-21.
ESH-ESC 2003.European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension[J].J Hypertens,21:1011-1053.
Fovaeus M,Andersson KE,Batra S,et al.1987.Effects of calcium,calcium channel blockers and Bay K 8644 on contractions induced by muscarinic receptor stimulation of isolated bladder muscle from rabbit and man[J].J Urol,137:798-803.
Ganitkevich VY,Isenberg G 1992.Contribution of Ca(2+)-induced Ca2+ release to the[Ca2+]i transients in myocytes from guinea-pig urinary bladder[J].J Physiol,458:119-137.
Gu D,Gupta A,Muntner P,et al.2005.Prevalence of cardiovascular disease risk factor clustering among the adult population of China:results from the International Collaborative Study of Cardiovascular Disease in Asia(InterAsia)[J].Circulation,112:658-665.
Hashitani H,Bramich NJ,Hirst GD 2000.Mechanisms of excitatory neuromuscular transmission in the guinea-pig urinary bladder[J].J Physiol,524 Pt 2:565-579.
Hosmane BS,Maurath CJ,Jordan DC,et al.1992.Effect of age and dose on the incidence of adverse events in the treatment of hypertension in patients receiving terazosin[J].J Clin Pharmacol,32:434-443.
Itskovitz HD 1994.Alpha 1-blockade for the treatment of hypertension:a megastudy of terazosin in 2214 clinical practice settings[J].Clin Ther,16:490-504.
Joseph MA,Harlow SD,Wei JT,et al.2003.Risk factors for lower urinary tract symptoms in a population-based sample of African-American men[J].Am J Epidemiol,157:906-914.
Kaplan SA,Roehrborn CG,Rovner ES,et al.2006.Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder:a randomized controlled trial[J].JAMA,296:2319-2328.
Lee JY,Kim HW,Lee SJ,et al.2004.Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder[J].BJU Int,94:817-820.
Lenz ML,Pool JL,Laddu AR,et al.1995.Combined terazosin and verapamil therapy in essential hypertension.Hemodynamic and pharmacokinetic interactions[J].Am J Hypertens,8:133-145.
Nalbantgil S,Nalbantgil I,Onder R 2000.Clinically additive effect between doxazosin and amlodipine in the treatment of essential hypertension[J].Am J Hypertens,13:921-926.
Parsons JK 2007.Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms:new approaches to old problems[J].J Urol,178:395-401.
Peili G,X C,H L,et al.2000.Clinical study of domestic terazosin on benign prostatic hyperplasia[J].Chin J Clin Pharmacol,16:338-341.
Pool JL 1991.Combination antihypertensive therapy with terazosin and other antihypertensive agents:results of clinical trials[J].Am Heart J,122:926-931.
Rohrmann S,Smit E,Giovannucci E,et al.2005.Association between markers of the metabolic syndrome and lower urinary tract symptoms in the Third National Health and Nutrition Examination Survey(NHANES Ⅲ)[J].Int J Obes(Lond),29:310-316.
Rosen R,Altwein J,Boyle P,et al.2003.Lower urinary tract symptoms and male sexual dysfunction:the multinational survey of the aging male(MSAM-7)[J].Eur Urol,44:637-649.
Tanaka Y,Masumori N,Itoh N,et al.2002.Urodynamic effects of terazosin treatment for Japanese patients with symptomatic benign prostatic hyperplasia[J].J Urol,167:2492-2495.
Teramoto N,Yunoki T,Ikawa S,et al.2001.The involvement of L-type Ca(2+) channels in the relaxant effects of the ATP-sensitive K(+) channel opener ZD6169 on pig urethral smooth muscle[J].Br J Pharmacol,134:1505-1515.
Thorpe A,Neal D 2003.Benign prostatic hyperplasia[J].Lancet,361:1359-1367.
Titmarsh S,Monk JP 1987.Terazosin.A review of its pharmacodynamic and pharmacokinetic properties,and therapeutic efficacy in essential hypertension[J].Drugs,33:461-477.
Tsujii T 2000.Comparison of prazosin,terazosin and tamsulosin in the treatment of symptomatic benign prostatic hyperplasia:a short-term open,randomized multicenter study.BPH Medical Therapy Study Group.Benign prostatic hyperplasia[J].Int J Urol,7:199-205.
Valle R,Semplicini A,Serena L,et al.1994.[Pressure and metabolic effects of terazosin in essential hypertension][J].Cardiologia,39:421-424.
Wegener JW,Schulla V,Lee TS,et al.2004.An essential role of Cav1.2 L-type calcium channel for urinary bladder function[J].FASEB J,18:1159-1161.
Wong SY,Woo J,Hong A,et al.2006.Risk factors for lower urinary tract symptoms in southern Chinese men[J].Urology,68:1009-1014.
Wu C,Sui G,Fry CH 2002.The role of the L-type Ca(2+) channel in refilling functional intracellular Ca(2+) stores in guinea-pig detrusor smooth muscle[J].J Physiol,538:357-369.
Wykretowicz A,Guzik P,Wysocki H 2008.Doxazosin in the current treatment of hypertension[J].Expert Opin Pharmacother,9:625-633.
Xu X,Niu T,Christiani DC,et al.1997.Environmental and occupational determinants of blood pressure in rural communities in China[J].Ann Epidemiol,7:95-106.
Yang Y,Zhao XF,Li HZ,et al.2007.Efficacy and safety of combined therapy with terazosin and tolteradine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia:a prospective study[J].Chin Med J(Engl),120:370-374.
Zusman RM 2000.The role of alpha 1-blockers in combination therapy for hypertension[J].Int J Clin Pract,54:36-40.
潘发明,徐希平2004.高血压的药物基因组学的研究进展[J].国外医学·遗传学分册,27:191-193.
Abrams P,Cardozo L,Fall M,et al.2003.The standardisation of terminology in lower urinary tract function:report from the standardisation sub-committee of the International Continence Society[J].Urology,61:37-49.
Abrams P,Andersson K,Brubaker L,2005.Recommendations of the International Scientific Committee:evaluation and treatment of urinary incontinence,pelvic organ prolapse and faecal incontinence[M],Vol.,Health Publication,Paris.
Abrams P,Andersson KE 2007.Muscarinic receptor antagonists for overactive bladder[J].BJU Int,100:987-1006.
ALLHAT-Collaborative-Research-Group 2000.Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone:the antihypertensive and lipid-lowering treatment to prevent heart attack trial(ALLHAT).ALLHAT Collaborative Research Group[J].JAMA,283:1967-1975.
Andersson K,Appell R,Cardozo L,2005.Pharmacological treatment of urinary incontinence[M],Vol.,Health Publication,Paris.
Arnett DK,Claas SA,Glasser SP 2006.Pharmacogenetics of antihypertensive treatment[J].Vascul Pharmacol,44:107-118.
AUA 2006.Management of BPH clinical guideline.2003.Updated 2006.http://www.auanet.org/guidelines/bph.cfm.
Badawi JK,Langbein S 2006a.Selective beta-adrenoceptor agonists,calcium antagonists and potassium channel openers as a possible medical treatment of the overactive bladder and urge incontinence[J].Pharmazie,61:175-178.
Badawi JK,Li H,Langbein S,et al.2006b.Inhibitory effects of L- and T-type calcium antagonists on contractions of human detrusor muscle[J].Eur J Clin Pharmacol,62:347-354.
Benedict NJ 2007.Sitaxsentan in the management of pulmonary arterial hypertension[J].Am J Health Syst Pharm,64:363-368.
Bengtsson K,Melander O,Orho-Melander M,et al.2001a.Polymorphism in the beta(1)-adrenergic receptor gene and hypertension[J].Circulation,104:187-190.
Bengtsson K,Orho-Melander M,Melander O,et al.2001b.Beta(2)-adrenergic receptor gene variation and hypertension in subjects with type 2 diabetes[J].Hypertension,37:1303-1308.
Bodeker J,Salim SA,Nagel R 1976.Nifedipine(a calcium antagonist) in the treatment of urinary obstruction[J].Dtsch Med Wochenschr,101:1866-1868.
Borjesson M,Magnusson Y,Hjalmarson A,et al.2000.A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure[J].Eur Heart J,21:1853-1858.
Braunwald E,Domanski MJ,Fowler SE,et al.2004.Angiotensin-converting-enzyme inhibition in stable coronary artery disease[J].N Engl J Med,351:2058-2068.
Bray MS,Krushkal J,Li L,et al.2000.Positional genomic analysis identifies the beta(2)-adrenergic receptor gene as a susceptibility locus for human hypertension[J].Circulation,101:2877-2882.
Bristow MR 1993.Changes in myocardial and vascular receptors in heart failure[J].J Am Coll Cardiol,22:61A-71A.
Brodde OE,Michel MC 1999.Adrenergic and muscarinic receptors in the human heart[J].Pharmacol Rev,51:651-690.
Bump R,Steers W,Herschorn S 2006.Duloxetine compared with placebo for the treatment of women with symptoms of bladder overactivity[J].Neurourol Urodyn,25:660-661.
Burgio KL 2004.Current perspectives on management of urgency using bladder and behavioral training[J].J Am Acad Nurse Pract,16:4-7.
Buscher R,Herrmann V,Ring KM,et al.1999.Variability in phenylephrine response and essential hypertension:a search for human alpha(1B)-adrenergic receptor polymorphisms[J].J Pharmacol Exp Ther,291:793-798.
Carbone A,Palleschi G,Conte A,et al.2006.Gabapentin treatment of neurogenic overactive bladder[J].Clin Neuropharmacol,29:206-214.
Chappie CR,Roehrborn CG 2006.A shifted paradigm for the further understanding,evaluation,and treatment of lower urinary tract symptoms in men:focus on the bladder[J].Eur Urol,49:651-658.
Chu FM,Dmochowski R 2006.Pathophysiology of overactive bladder[J].Am J Med,119:3-8.
Cifkova R,Erdine S,Fagard R,et al.2003.Practice guidelines for primary care physicians:2003 ESH/ESC hypertension guidelines[J].J Hypertens,21:1779-1786.
Cockayne DA,Hamilton SG,Zhu QM,et al.2000.Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice[J].Nature,407:1011-1015.
Cohn JN,Tognoni G 2001.A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure[J].N Engl J Med,345:1667-1675.
CUA 2007.Chinese Urological Association Guidelines on Managements of urinary diseases.Available at:http://www.cuan.cn/cnspro/WebDiseaseGuide.aspx.
Dahlof B,Sever PS,Poulter NR,et al.2005.Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required,in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood
Pressure Lowering Arm(ASCOT-BPLA):a multicentre randomised controlled trial[J].Lancet,366:895-906.
Dmochowski RR,Sanders SW,Appell RA,et al.2005.Bladder-health diaries:an assessment of 3-day vs 7-day entries[J].BJU Int,96:1049-1054.
Doulton TW,He FJ,MacGregor GA 2005.Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension[J].Hypertension,45:880-886.
Drysdale CM,McGraw DW,Stack CB,et al.2000.Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness[J].Proc Natl Acad Sci USA,97:10483-10488.
EAU 2004.EAU guidelines on benign prostatic hyperplasia.http://www.uroweb.org/fileadmin/user_upload/Guidelines/BPH.pdf.
Epstein BJ,Gums JG 2005.Can the renin-angiotensin system protect against stroke?A focus on angiotensin Ⅱ receptor blockers[J].Pharmacotherapy,25:531-539.
Feldman RD,Gros R 1998.Impaired vasodilator function in hypertension:the role of alterations in receptor-G protein coupling[J].Trends Cardiovasc Med,8:297-305.
Fossum E,Berge KE,Hoieggen A,et al.2001.Polymorphisms in candidate genes for blood pressure regulation in young men with normal or elevated screening blood pressure[J].Blood Press,10:92-100.
Fournier A,Messerli FH,Achard JM,et al.2004.Cerebroprotection mediated by angiotensin Ⅱ:a hypothesis supported by recent randomized clinical trials[J].J Am Coll Cardiol,43:1343-1347.
Fovaeus M,Andersson KE,Batra S,et al.1987.Effects of calcium,calcium channel blockers and Bay K 8644 on contractions induced by muscarinic receptor stimulation of isolated bladder muscle from rabbit and man[J].J Urol,137:798-803.
Fowler FJ,Jr.,Wennberg JE,Timothy RP,et al.1988.Symptom status and quality of life following prostatectomy[J].JAMA,259:3018-3022.
Fox KM 2003.Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease:randomised,double-blind,placebo-controlled,multicentre trial (the EUROPA study)[J].Lancet,362:782-788.
Fujisawa T,Ikegami H,Yamato E,et al.1997.Trp64Arg mutation of beta3-adrenergic receptor in essential hypertension:insulin resistance and the adrenergic system[J].Am J Hypertens,10:101-105.
Furberg CD,Psaty BM,Meyer JV 1995.Nifedipine.Dose-related increase in mortality in patients with coronary heart disease[J].Circulation,92:1326-1331.
Fuster V,Wayne A,O'Rourke R,2004.Hurst's The Heart[M],Vol.11th edn,McGraw-Hill,New York.
Ganitkevich VY,Isenberg G 1992.Contribution of Ca(2+)-induced Ca2+ release to the[Ca2+]i transients in myocytes from guinea-pig urinary bladder[J].J Physiol,458:119-137.
Gauthier C,Langin D,Balligand JL 2000a.Beta3-adrenoceptors in the cardiovascular system[J].Trends Pharmacol Sci,21:426-431.
Gauthier C,Leblais V,Moniotte S,et al.2000b.The negative inotropic action of catecholamines:role of beta3-adrenoceptors[J].Can J Physiol Pharmacol,78:681-690.
Golomb E,Rosenzweig N,Eilam R,et al.2000.Spontaneous hyperplasia of the ventral lobe of the prostate in aging genetically hypertensive rats[J].J Androl,21:58-64.
Granneman JG,Lahners KN,Rao DD 1992.Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block[J].Mol Pharmacol,42:964-970.
Gu D,Gupta A,Muntner P,et al.2005.Prevalence of cardiovascular disease risk factor clustering among the adult population of China:results from the International Collaborative Study of Cardiovascular Disease in Asia(InterAsia)[J].Circulation,112:658-665.
Hahntow IN,Koopmans RP,Michel MC 2006.The beta2-adrenoceptor gene and hypertension:is it the promoter or the coding region or neither?[J].J Hypertens,24:1003-1007.
Hannestad YS,Rortveit G,Daltveit AK,et al.2003.Are smoking and other lifestyle factors associated with female urinary incontinence?The Norwegian EPINCONT Study[J].BJOQ 110:247-254.
Hashim H,Malmberg L,Graugaard-Jensen C 2006.Abstracts of the International Continence Society 36th Annual Meeting,Christchurch,New Zealand,27 November-1 December 2006[J].Neurourol Urodyn,25:507-671.
Hashitani H,Bramich NJ,Hirst GD 2000.Mechanisms of excitatory neuromuscular transmission in the guinea-pig urinary bladder[J].J Physiol,524 Pt 2:565-579.
Hawkins GA,Tantisira K,Meyers DA,et al.2006.Sequence,haplotype,and association analysis of ADRbeta2 in a multiethnic asthma case-control study[J].Am J Respir Crit Care Med,174:1101-1109.
Herrmann SM,Nicaud V,Tiret L,et al.2002.Polymorphisms of the beta2-adrenoceptor(ADRB2) gene and essential hypertension:the ECTIM and PEGASE studies[J].J Hypertens,20:229-235.
Herrmann V,Buscher R,Go MM,et al.2000.Beta2-adrenergic receptor polymorphisms at codon 16,cardiovascular phenotypes and essential hypertension in whites and African Americans[J].Am J Hypertens,13:1021-1026.
Homma Y,Kawabe K,Tsukamoto T,et al.1997.Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score[J].Int J Urol,4:40-46.
Huang K,Shi Y,Tang W,et al.2008.No association found between the promoter variants of ADRA1A and schizophrenia in the Chinese population[J].J Psychiatr Res,42:384-388.
Iaccarino G,Lanni F,Cipolletta E,et al.2004.The Glu27 allele of the beta2 adrenergic receptor increases the risk of cardiac hypertrophy in hypertension[J].J Hypertens,22:2117-2122.
Iaccarino G,Izzo R,Trimarco V,et al.2006.Beta2-adrenergic receptor polymorphisms and treatment-induced regression of left ventricular hypertrophy in hypertension[J].Clin Pharmacol Ther,80:633-645.
Jardin A,Bensadoun H,Delauche-Cavallier MC,et al.1994.Long-term treatment of benign prostatic hyperplasia with alfuzosin:a 24-30 month survey.BPHALF Group[J].Br J Urol,74:579-584.
Johnson JA,Terra SG 2002.Beta-adrenergic receptor polymorphisms:cardiovascular disease associations and pharmacogenetics[J].Pharm Res,19:1779-1787.
Jolleys JV,Donovan JL,Nanchahal K,et al.1994.Urinary symptoms in the community:how bothersome are they?[J].Br J Urol,74:551-555.
Joseph MA,Harlow SD,Wei JT,et al.2003.Risk factors for lower urinary tract symptoms in a population-based sample of African-American men[J].Am J Epidemiol,157:906-914.
Julius S,Kjeldsen SE,Weber M,et al.2004.Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine:the VALUE randomised trial[J].Lancet,363:2022-2031.
Julius S,Weber MA,Kjeldsen SE,et al.2006.The Valsartan Antihypertensive Long-Term Use Evaluation(VALUE) trial:outcomes in patients receiving mono therapy[J].Hypertension,48:385-391.
Kajioka S,Nakayama S,McMurray G,et al.2002.Ca(2+) channel properties in smooth muscle cells of the urinary bladder from pig and human[J].Eur J Pharmacol,443:19-29.
Kaplan SA,Bowers DL,Te AE,et al.1996.Differential diagnosis of prostatism:A 12-year retrospective analysis of symptoms,urodynamics and satisfaction with therapy[J].J Urol,155:1305-1308.
Kaplan SA,Roehrborn CG,Rovner ES,et al.2006.Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder:a randomized controlled trial[J].JAMA,296:2319-2328.
Kirstein SL,Insel PA 2004.Autonomic nervous system pharmacogenomics:a progress report[J].Pharmacol Rev,56:31-52.
Kjeldsen SE,Julius S,Mancia G,et al.2006.Effects of valsartan compared to amlodipine on preventing type 2 diabetes in high-risk hypertensive patients:the VALUE trial[J].J Hypertens,24:1405-1412.
Knutson T,Pettersson S,Dahlstrand C 2001.Pressure-flow studies for patient selection in the treatment of symptomatic BPH-a one-year follow-up study[J].Scand J Urol Nephrol,35:470-475.
Krum H,Gilbert RE 2007.Novel therapies blocking the renin-angiotensin-aldosterone system in the management of hypertension and related disorders[J].J Hypertens,25:25-35.
Lee JY,Kim HW,Lee SJ,et al.2004.Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder[J].BJU Int,94:817-820.
Leenen FH,Nwachuku CE,Black HR,et al.2006.Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial[J].Hypertension,48:374-384.
Lei B,Morris DP,Smith MP,et al.2005.Novel human alphala-adrenoceptor single nucleotide polymorphisms alter receptor pharmacology and biological function[J].Naunyn Schmiedebergs Arch Pharmacol,371:229-239.
Lelias JM,Kaghad M,Rodriguez M,et al.1993.Molecular cloning of a human beta 3-adrenergic receptor cDNA[J].FEBS Lett,324:127-130.
Levin R,Chichester P,Hass M,et al.2002.Obstructive bladder dysfunction:morphological, biochemical and molecular changes[J].Eur Urol Suppl,1:14-20.
Liggett SB,Wagoner LE,Craft LL,et al.1998.The Ilel64 beta2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure[J].J Clin Invest,102:1534-1539.
Liggett SB 2000a.The pharmacogenetics of beta2-adrenergic receptors:relevance to asthma[J].J Allergy Clin Immunol,105:S487-492.
Liggett SB 2000b.beta(2)-adrenergic receptor pharmacogenetics[J].Am J Respir Crit Care Med,161:S197-201.
Lima JJ,Holbrook JT,Wang J,et al.2006.The C523A beta2 adrenergic receptor polymorphism associates with markers of asthma severity in African Americans[J].J Asthma,43:185-191.
Liu L,Zhang Y,Liu G,et al.2005.The Felodipine Event Reduction(FEVER) Study:a randomized long-term placebo-controlled trial in Chinese hypertensive patients[J].J Hypertens,23:2157-2172.
MacKinnon M,Shurraw S,Akbari A,et al.2006.Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease:a systematic review of the efficacy and safety data[J].Am J Kidney Dis,48:8-20.
MacMahon S 1990.Antihypertensive drug treatment:the potential,expected and observed effects on vascular disease[J].J Hypertens Suppl,8:S239-244.
Maggi CA,Giuliani S,Patacchini R,et al.1989.Multiple sources of calcium for contraction of the human urinary bladder muscle[J].Br J Pharmacol,98:1021-1031.
Malacco E,Vari N,Capuano V,et al.2003.A randomized,double-blind,active-controlled,parallel-group comparison of valsartan and amlodipine in the treatment of isolated systolic hypertension in elderly patients:the Val-Syst study[J].Clin Ther,25:2765-2780.
Marinese D,Patel R,Walden PD 2003.Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice[J].Prostate,54:230-237.
Maruenda J,Bhatnagar V,Lowenthal DT 1999.Hypertension in the elderly with coexisting benign prostatic hyperplasia[J].Urology,53:7-12;discussion 12-13,41-12.
Masaki T 1995.Possible role of endothelin in endothelial regulation of vascular tone[J].Annu Rev Pharmacol Toxicol,35:235-255.
Mason RP,Marche P,Hintze TH 2003.Novel vascular biology of third-generation L-type calcium channel antagonists:ancillary actions of amlodipine[J].Arterioscler Thromb Vasc Biol,23:2155-2163.
Matityahou A,Rosenzweig N,Golomb E 2003.Rapid proliferation of prostatic epithelial cells in spontaneously hypertensive rats:a model of spontaneous hypertension and prostate hyperplasia[J].J Androl,24:263-269.
McCaffery JM,Pogue-Geile MF,Ferrell RE,et al.2002.Variability within alpha-and beta-adrenoreceptor genes as a predictor of cardiovascular function at rest and in response to mental challenge[J].J Hypertens,20:1105-1114.
McCall KL,Craddock D,Edwards K 2006.Effect of angiotensin-converting enzyme inhibitors and angiotensin Ⅱ type 1 receptor blockers on the rate of new-onset diabetes mellitus:a review and pooled analysis[J].Pharmacotherapy,26:1297-1306.
McKelvie RS,Yusuf S,Pericak D,et al.1999.Comparison of candesartan,enalapril,and their combination in congestive heart failure:randomized evaluation of strategies for left ventricular dysfunction(RESOLVD) pilot study.The RESOLVD Pilot Study Investigators[J].Circulation,100:1056-1064.
McMurray JJ,Ostergren J,Swedberg K,et al.2003.Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors:the CHARM-Added trial[J].Lancet,362:767-771.
McVary KT 2006.BPH:epidemiology and comorbidities[J].Am J Manag Care,12:S122-128.
Messerli FH 2002.Vasodilatory edema:a common side effect of antihypertensive therapy[J].Curr Cardiol Rep,4:479-482.
Messerli FH,Weir MR,Neutel JM 2002.Combination therapy of amlodipine/benazepril versus monotherapy of amlodipine in a practice-based setting[J].Am J Hypertens,15:550-556.
Michel MC,Heemann U,Schumacher H,et al.2004.Association of hypertension with symptoms of benign prostatic hyperplasia[J].J Urol,172:1390-1393.
Milsom I,Abrams P,Cardozo L,et al.2001.How widespread are the symptoms of an overactive bladder and how are they managed?A population-based prevalence study[J].BJU Int,87:760-766.
Mochtar CA,Laan W,Van Houwelingen KP,et al.2006.Polymorphisms in the alpha1A-adrenoceptor gene do not modify the short-and long-term efficacy of alpha1-adrenoceptor antagonists in the treatment of benign prostatic hyperplasia[J].BJU Int,97:852-855.
Moore JD,Mason DA,Green SA,et al.1999.Racial differences in the frequencies of cardiac beta(1)-adrenergic receptor polymorphisms:analysis of c145A＞G and c1165G＞C[J].Hum Mutat,14:271.
Moorthy P,Lapitan MC,Quek PL,et al.2004.Prevalence of overactive bladder in Asian men:an epidemiological survey[J].BJU Int,93:528-531.
Moosmang S,Lenhardt P,Haider N,et al.2005.Mouse models to study L-type calcium channel function[J].Pharmacol Ther,106:347-355.
Nalbantgil S,Nalbantgil I,Onder R 2000.Clinically additive effect between doxazosin and amlodipine in the treatment of essential hypertension[J].Am J Hypertens,13:921-926.
NCBI dbSNP database[J].
Nicolas Torralba JA,Tornero Ruiz J,Banon Perez V,et al.2003.Relation between hypertension and clinical cases of benign prostatic hyperplasia[J].Arch Esp Urol,56:355-358.
NIH Management of hypertension in adults in primary care:partial update.The National Institute for Health and Clinical Excellence[online][J].Available from URL:http://www.nice.org.uk/guidance/CG34.
Nissen SE,Tuzcu EM,Libby P,et al.2004a.Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure:the CAMELOT study:a randomized controlled trial[J].JAMA,292:2217-2225.
Nissen SE,Tuzcu EM,Schoenhagen P,et al.2004b.Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis:a randomized controlled trial[J].JAMA,291:1071-1080.
Nonen S,Okamoto H,Fujio Y,et al.2008.Polymorphisms of norepinephrine transporter and adrenergic receptor alpha ID are associated with the response to beta-blockers in dilated cardiomyopathy[J].Pharmacogenomics J,8:78-84.
Nowara A,Witek A,Wilk K 2007.[Diagnostic and treatment of overactive bladder][J].Ginekol Pol,78:549-553.
O'Sullivan M,Murphy C,Deasy C,et al.2004.Effects of transurethral resection of prostate on the quality of life of patients with benign prostatic hyperplasia[J].J Am Coll Surg,198:394-403.
Ouslander JG 2004.Management of overactive bladder[J].N Engl J Med,350:786-799.
Parsons JK 2007.Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms:new approaches to old problems[J].J Urol,178:395-401.
Peters TJ,Donovan JL,Kay HE,et al.1997.The International Continence Society“Benign Prostatic Hyperplasia”Study:the botherosomeness of urinary symptoms[J].J Urol,157:885-889.
Pinggera GM,Mitterberger M,Steiner E,et al.2008.Association of lower urinary tract symptoms and chronic ischaemia of the lower urinary tract in elderly women and men:assessment using colour Doppler ultrasonography[J].BJU Int,102:470-474.
Podlowski S,Wenzel K,Luther HP,et al.2000.Betal-adrenoceptor gene variations:a role in idiopathic dilated cardiomyopathy?[J].J Mol Med,78:87-93.
Poldermans D,Gamboa R,Fomina I 2006.Comparative safety and blood pressure-lowering efficacy of a combination of amlodipine/valsartan and lisinopril/HCTZ in patients with stage 2 hypertension[abstract P-217].Presented at American Society of Hypertension;New York (NY);[J].
Pool JL 1991.Combination antihypertensive therapy with terazosin and other antihypertensive agents:results of clinical trials[J].Am Heart J,122:926-931.
Pool JL,Schmieder RE,Azizi M,et al.2007.Aliskiren,an orally effective renin inhibitor,provides antihypertensive efficacy alone and in combination with valsartan[J].Am J Hypertens,20:11-20.
Poole-Wilson PA,Lubsen J,Kirwan BA,et al.2004.Effect of long-acting nifedipine on
mortality and cardiovascular morbidity in patients with stable angina requiring treatment(ACTION trial):randomised controlled trial[J].Lancet,364:849-857.
Port JD,Bristow MR 2001.Altered beta-adrenergic receptor gene regulation and signaling in chronic heart failure[J].J Mol Cell Cardiol,33:887-905.
Poulter NR,Wedel H,Dahlof B,et al.2005.Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes
Trial-Blood Pressure Lowering Arm(ASCOT-BPLA)[J].Lancet,366:907-913.
Psaty BM,Smith NL,Siscovick DS,et al.1997.Health outcomes associated with antihypertensive therapies used as first-line agents.A systematic review and meta-analysis[J].JAMA,277:739-745.
Rocha R,Williams GH 2002.Rationale for the use of aldosterone antagonists in congestive heart failure[J].Drugs,62:723-731.
Rohrmann S,Smit E,Giovannucci E,et al.2005.Association between markers of the metabolic syndrome and lower urinary tract symptoms in the Third National Health and Nutrition Examination Survey(NHANES III)[J].Int J Obes(Lond),29:310-316.
Rosen R,Altwein J,Boyle P,et al.2003.Lower urinary tract symptoms and male sexual dysfunction:the multinational survey of the aging male(MSAM-7)[J].Eur Urol,44:637-649.
Rosmond R,Ukkola O,Chagnon M,et al.2000.Polymorphisms of the beta2-adrenergic receptor gene(ADRB2) in relation to cardiovascular risk factors in men[J].J Intern Med,248:239-244.
Rud T,Andersson KE,Ulmsten U 1979.Effects of nifedipine in women with unstable bladders[J].Urol Int,34:421-429.
Rudolph AE,Rocha R,McMahon EG 2004.Aldosterone target organ protection by eplerenone[J].Mol Cell Endocrinol,217:229-238.
Schelleman H,Klungel OH,van Duijn CM,et al.2006.Drug-gene interaction between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and antihypertensive therapy[J],Ann Pharmacother,40:212-218.
Sehti A,Tybjaerg-Hansen A,Jensen G,et al.2005.164Ile allele in the(32-adrenergic receptor gene is associated with risk of elevated blood pressure in women.The Copenhagen City Heart Study.[J].Pharmacogenet Genom,15:633-645.
Sellers DJ,McKay N 2007.Developments in the pharmacotherapy of the overactive bladder[J].Curr Opin Urol,17:223-230.
Shioji K,Kokubo Y,Mannami T,et al.2004.Association between hypertension and the alpha-adducin,betal-adrenoreceptor,and G-protein beta3 subunit genes in the Japanese population;the Suita study[J].Hypertens Res,27:31-37.
Sica DA 2002.Rationale for fixed-dose combinations in the treatment of hypertension:the cycle repeats[J].Drugs,62:443-462.
Sica DA 2003.Combination angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy:its role in clinical practice[J].J Clin Hypertens(Greenwich),5:414-420.
Small KM,Wagoner LE,Levin AM,et al.2002.Synergistic polymorphisms of betal-and alpha2C-adrenergic receptors and the risk of congestive heart failure[J].N Engl J Med,347:1135-1142.
Snapir A,Heinonen P,Tuomainen TP,et al.2001.An insertion/deletion polymorphism in the alpha2B-adrenergic receptor gene is a novel genetic risk factor for acute coronary events[J].J Am Coll Cardiol,37:1516-1522.
Snapir A,Koskenvuo J,Toikka J,et al.2003a.Effects of common polymorphisms in the alpha 1A-,alpha2B-,betal-and beta2-adrenoreceptors on haemodynamic responses to adrenaline[J].Clin Sci(Lond),104:509-520.
Snapir A,Scheinin M,Groop LC,et al.2003b.The insertion/deletion variation in the alpha2B-adrenoceptor does not seem to modify the risk for acute myocardial infarction,but may modify the risk for hypertension in sib-pairs from families with type 2 diabetes[J].Cardiovasc Diabetol,2:15.
Sofowora GG,Dishy V,Landau R,et al.2004.Alpha 1A-adrenergic receptor polymorphism and vascular response[J].Clin Pharmacol Ther,75:539-545.
Srikrishna S,Robinson D,Cardozo L,et al.2007.Management of overactive bladder syndrome[J].Postgrad Med J,83:481-486.
Staessen JA,Li Y,Richart T 2006.Oral renin inhibitors[J].Lancet,368:1449-1456.
Stergiou GS,Makris T,Papavasiliou M,et al.2005.Comparison of antihypertensive effects of an angiotensin-converting enzyme inhibitor,a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocker monotherapy[J].J Hypertens,23:883-889.
Stewart WF,Van Rooyen JB,Cundiff GW,et al.2003.Prevalence and burden of overactive bladder in the United States[J].World J Urol,20:327-336.
Strazzullo P,lacone R,Siani A,et al.2001.Relationship of the Trp64Arg polymorphism of the beta3-adrenoceptor gene to central adiposity and high blood pressure:interaction with age.Cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study[J].J Hypertens,19:399-406.
Sugaya K,Kadekawa K,Ikehara A,et al.2003.Influence of hypertension on lower urinary tract symptoms in benign prostatic hyperplasia[J].Int J Urol,10:569-574;discussion 575.
Swithinbank L,Hashim H,Abrams P 2005.The effect of fluid intake on urinary symptoms in women[J].J Urol,174:187-189.
Taylor JA,Hand GA,Johnson DG,et al.1992.Augmented forearm vasoconstriction during dynamic exercise in healthy older men[J].Circulation,86:1789-1799.
Taylor M,Bristow M 2004a.The emerging pharmacogenomics of the betaadrenergic receptors[J].Congest Heart Fail,10:281-288.
Taylor MR,Bristow MR 2004b.The emerging pharmacogenomics of the beta-adrenergic receptors[J].Congest Heart Fail,10:281-288.
Teramoto N,Yunoki T,Ikawa S,et al.2001.The involvement of L-type Ca(2+) channels in the relaxant effects of the ATP-sensitive K(+) channel opener ZD6169 on pig urethral smooth muscle[J].Br J Pharmacol,134:1505-1515.
Tesson F,Charron P,Peuchmaurd M,et al.1999.Characterization of a unique genetic variant in the beta 1-adrenoceptor gene and evaluation of its role in idiopathic dilated cardiomyopathy.CARDIGENE Group[J].J Mol Cell Cardiol,31:1025-1032.
Tonolo G,Melis MG,Secchi G,et al.1999.Association of Trp64Arg beta 3-adrenergic-receptor gene polymorphism with essential hypertension in the Sardinian population[J].J Hypertens,17:33-38.
Trotta R,Donati MB,Iacoviello L 2004.Trends in pharmacogenomics of drugs acting on hypertension[J].Pharmacol Res,49:351-356.
Turnbull F 2003.Effects of different blood-pressure-lowering regimens on major cardiovascular events:results of prospectively-designed overviews of randomised trials[J].Lancet,362:1527-1535.
Turner ST,Schwartz GL 2005.Gene markers and antihypertensive therapy[J].Curr Hypertens Rep,7:21-30.
Unwala DJ,Barboglio P,Gousse AE 2007.Repeated botulinum toxin injection for idiopathic overactive bladder:will chemodenervation become a long-term solution?[J].Curr Urol Rep,8:419-424.
van Spronsen A,Nahmias C,Krief S,et al.1993.The promoter and intron/exon structure of the human and mouse beta 3-adrenergic-receptor genes[J].Eur J Biochem,213:1117-1124.
Vendrell J,Gutierrez C,Broch M,et al.1998.Beta 3-adrenoreceptor gene polymorphism and leptin.Lack of relationship in type 2 diabetic patients[J].Clin Endocrinol(Oxf),49:679-683.
Von Wowern F,Bengtsson K,Lindblad U,et al.2004.Functional variant in the(alpha)2B adrenoceptor gene,a positional candidate on chromosome 2,associates with hypertension[J].Hypertension,43:592-597.
Weber MA,Julius S,Kjeldsen SE,et al.2004.Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial[J].Lancet,363:2049-2051.
Wegener JW,Schulla V,Lee TS,et al.2004.An essential role of Cav1.2 L-type calcium channel for urinary bladder function[J].FASEB J,18:1159-1161.
Weiser M,Frishman WH,Michaelson MD,et al.1997.The pharmacologic approach to the treatment of obesity[J].J Clin Pharmacol,37:453-473.
Whelton PK,Barzilay J,Cushman WC,et al.2005.Clinical outcomes in antihypertensive treatment of type 2 diabetes,impaired fasting glucose concentration,and normoglycemia:Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial(ALLHAT)[J].Arch Intern Med,165:1401-1409.
Whitworth JA 2003.2003 World Health Organization(WHO)/International Society of Hypertension(ISH) statement on management of hypertension[J].J Hypertens,21:1983-1992.
WHO,2002.Reducing Risks,Promoting Life[M],Vol.,World Health Organization,Geneva,Switzerland.
Wong SY,Woo J,Hong A,et al.2006.Risk factors for lower urinary tract symptoms in southern Chinese men[J].Urology,68:1009-1014.
Wu C,Sui G,Fry CH 2002.The role of the L-type Ca(2+) channel in refilling functional intracellular Ca(2+) stores in guinea-pig detrusor smooth muscle[J].J Physiol,538:357-369.
Wu H,Tang W,Li H,et al.2006.Association of the beta2-adrenergic receptor gene with essential hypertension in the non-Han Chinese Yi minority human population[J].J Hypertens,24:1041-1047.
Xie HG,Stein CM,Kim RB,et al.1999.Frequency of functionally important beta-2 adrenoceptor polymorphisms varies markedly among African-American,Caucasian and Chinese individuals[J].Pharmacogenetics,9:511-516.
Yamada K,Ishiyama-Shigemoto S,Ichikawa F,et al.1999.Polymorphism in the 5'-leader cistron of the beta2-adrenergic receptor gene associated with obesity and type 2 diabetes[J].J Clin Endocrinol Metab,84:1754-1757.
Yanagisawa M,Kurihara H,Kimura S,et al.1988.A novel potent vasoconstrictor peptide produced by vascular endothelial cells[J].Nature,332:411-415.
Yusuf S,Sleight P,Pogue J,et al.2000.Effects of an angiotensin-converting-enzyme inhibitor,ramipril,on cardiovascular events in high-risk patients.The Heart Outcomes Prevention Evaluation Study Investigators[J].N Engl J Med,342:145-153.
Zanchetti A,Rosei EA,Dal Palu C,et al.1998.The Verapamil in Hypertension and Atherosclerosis Study(VHAS):results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness[J].J Hypertens,16:1667-1676.
Zanchetti A,Bond MG,Hennig M,et al.2002.Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis:principal results of the European Lacidipine Study on Atherosclerosis(ELSA),a randomized,double-blind,long-term trial[J].Circulation,106:2422-2427.
Zhang H,Li X,Huang J,et al.2005.Cardiovascular and metabolic phenotypes in relation to the ADRA2B insertion/deletion polymorphism in a Chinese population[J].J Hypertens,23:2201-2207.
Zillich AJ,Garg J,Basu S,et al.2006.Thiazide diuretics,potassium,and the development of diabetes:a quantitative review[J].Hypertension,48:219-224.
Banzet O,Colin JN,Thibonnier M,et al.1983.Acute antihypertensive effect and pharmacokinetics of a tablet preparation of nifedipine[J].Eur J Clin Pharmacol,24:145-150.
Benetos A,Cambien F,Gautier S,et al.1996.Influence of the angiotensin Ⅱ type 1 receptor gene polymorphism on the effects of perindopril and nitrendipine on arterial stiffness in hypertensive individuals[J].Hypertension,28:1081-1084.
Brown MJ,Palmer CR,Castaigne A,et al.2000.Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study:Intervention as a Goal in Hypertension Treatment (INSIGHT)[J].Lancet,356:366-372.
Chung M,Reitberg D,Gaffney M,et al.1987.Clinical pharmacokinetics of nifedipine gastrointestinal therapeutic system.A controlled-release formulation of nifedipine[J].Am J Med,83:10-14.
Cockcroft JR,Gazis AG,Cross DJ,et al.2000.Beta(2)-adrenoceptor polymorphism determines vascular reactivity in humans[J].Hypertension,36:371-375.
Dishy V,Sofowora GG,Xie HG,et al.2001.The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization[J].N Engl J Med,345:1030-1035.
Dudley C,Keavney B,Casadei B,et al.1996.Prediction of patient responses to antihypertensive drugs using genetic polymorphisms:investigation of renin-angiotensin system genes[J].J Hypertens,14:259-262.
Eckert RE,Karsten AJ,Utz J,et al.2000.Regulation of renal artery smooth muscle tone by alphal-adrenoceptors:role of voltage-gated calcium channels and intracellular calcium stores[J].Urol Res,28:122-127.
Eichler HG,Blaschke TF,Hoffman BB 1990.Decreased responsiveness of superficial hand veins to phenylephrine in black normotensive males[J].J Cardiovasc Pharmacol,16:177-181.
Garovic VD,Joyner MJ,Dietz NM,et al.2003.Beta(2)-adrenergic receptor polymorphism and nitric oxide-dependent forearm blood flow responses to isoproterenol in humans[J].J Physiol,546:583-589.
Gratze G,Fortin J,Labugger R,et al.1999.beta-2 Adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians[J].Hypertension,33:1425-1430.
Green SA,Turki J,Innis M,et al.1994.Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties[J].Biochemistry, 33:9414-9419.
Han C,Abel PW,Minneman KP 1987.Alpha 1-adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle[J].Nature,329:333-335.
Han C,Li J,Minneman KP 1990.Subtypes of alpha 1-adrenoceptors in rat blood vessels[J].Eur J Pharmacol,190:97-104.
Hingorani AD,Jia H,Stevens PA,et al.1995.Renin-angiotensin system gene polymorphisms influence blood pressure and the response to angiotensin converting enzyme inhibition[J].J Hypertens,13:1602-1609.
Hoit BD,Suresh DP,Craft L,et al.2000.beta2-adrenergic receptor polymorphisms at amino acid 16 differentially influence agonist-stimulated blood pressure and peripheral blood flow in normal individuals[J].Am Heart J,139:537-542.
Krakoff LR 1993.Effectiveness of nifedipine gastrointestinal therapeutic system for treatment of hypertension:results of the MATH Trial[J].J Cardiovasc Pharmacol,21 Suppl 2:S14-17.
Liljedahl U,Karlsson J,Melhus H,et al.2003.A microarray minisequencing system for pharmacogenetic profiling of antihypertensive drug response[J].Pharmacogenetics,13:7-17.
Moffett S,Mouillac B,Bonin H,et al.1993.Altered phosphorylation and desensitization patterns of a human beta 2-adrenergic receptor lacking the palmitoylated Cys341[J].EMBO J,12:349-356.
Nair R,Dyer DC 1996.Pharmacological characterization of alpha 1-adrenoceptors in porcine uterine artery[J].Eur J Pharmacol,312:45-51.
O'Dowd BF,Hnatowich M,Regan JW,et al.1988.Site-directed mutagenesis of the cytoplasmic domains of the human beta 2-adrenergic receptor.Localization of regions involved in G protein-receptor coupling[J].J Biol Chem,263:15985-15992.
Psaty BM,Smith NL,Heckbert SR,et al.2002.Diuretic therapy,the alpha-adducin gene variant,and the risk of myocardial infarction or stroke in persons with treated hypertension[J].JAMA,287:1680-1689.
Rokosh DG,Simpson PC 2002.Knockout of the alpha 1A/C-adrenergic receptor subtype:the alpha 1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure[J].Proc Natl Acad Sci U S A,99:9474-9479.
Rudner XL,Berkowitz DE,Booth JV,et al.1999.Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age[J].Circulation,100:2336-2343.
Shibata K,Hirasawa A,Moriyama N,et al.1996.Alpha 1a-adrenoceptor polymorphism:pharmacological characterization and association with benign prostatic hypertrophy[J].Br J Pharmacol,118:1403-1408.
Sofowora GG,Dishy V,Landau R,et al.2004.Alpha 1A-adrenergic receptor polymorphism and vascular response[J].Clin Pharmacol Ther,75:539-545.
Soons PA,Schoemaker HC,Cohen AF,et al.1992.Intraindividual variability in nifedipine pharmacokinetics and effects in healthy subjects[J].J Clin Pharmacol,32:324-331.
Stein CM,Lang CC,Singh I,et al.2000.Increased vascular adrenergic vasoconstriction and decreased vasodilation in blacks.Additive mechanisms leading to enhanced vascular reactivity[J].Hypertension,36:945-951.
Taburet AM,Singlas E,Colin JN,et al.1983.Pharmacokinetic studies of nifedipine tablet.Correlation with antihypertensive effects[J].Hypertension,5:1129-33.
Testa R,Guarneri L,Taddei C,et al.1996.Functional antagonistic activity of Rec 15/2739,a novel alpha-1 antagonist selective for the lower urinary tract,on noradrenaline-induced contraction of human prostate and mesenteric artery[J].J Pharmacol Exp Ther,277:1237-1246.
Turner ST,Chapman AB,Schwartz GL,et al.2003.Effects of endothelial nitric oxide synthase,alpha-adducin,and other candidate gene polymorphisms on blood pressure response to hydrochlorothiazide[J].Am J Hypertens,16:834-839.
Villalobos-Molina R,Lopez-Guerrero JJ,Ibarra M 1997.Alpha ID-and alpha 1 A-adrenoceptors mediate contraction in rat renal artery[J].Eur J Pharmacol,322:225-227.
Xie HG,Kim RB,Stein CM,et al.1999.AlphalA-adrenergic receptor polymorphism:association with ethnicity but not essential hypertension[J].Pharmacogenetics,9:651-656
Badawi JK,Li H,Langbein S,et al.2006.Inhibitory effects of L-and T-type calcium antagonists on contractions of human detrusor muscle[J].Eur J Clin Pharmacol,62:347-354.
Bouchelouche K,Andersen L,Alvarez S,et al.2005.Increased contractile response to phenylephrine in detrusor of patients with bladder outlet obstruction:effect of the alpha1A and alpha1D-adrenergic receptor antagonist tamsulosin[J].J Urol,173:657-661.
Chappie CR,Roehrborn CG 2006.A shifted paradigm for the further understanding,evaluation,and treatment of lower urinary tract symptoms in men:focus on the bladder[J].Eur Urol,49:651-658.
Cifkova R,Erdine S,Fagard R,et al.2003.Practice guidelines for primary care physicians:2003 ESH/ESC hypertension guidelines[J].J Hypertens,21:1779-1786.
Das AK,Leggett RE,Whitbeck C,et al.2002.Effect of doxazosin on rat urinary bladder function after partial outlet obstruction[J].Neurourol Urodyn,21:160-166.
Fovaeus M,Andersson KE,Batra S,et al.1987.Effects of calcium,calcium channel blockers and Bay K 8644 on contractions induced by muscarinic receptor stimulation of isolated bladder muscle from rabbit and man[J].J Urol,137:798-803.
Ganitkevich VY,Isenberg G 1992.Contribution of Ca(2+)-induced Ca2+ release to the[Ca2+]i transients in myocytes from guinea-pig urinary bladder[J].J Physiol,458:119-137.
Goepel M,Wittmann A,Rubben H,et al.1997.Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate[J].Urol Res,25:199-206.
Hashitani H,Bramich NJ,Hirst GD 2000.Mechanisms of excitatory neuromuscular transmission in the guinea-pig urinary bladder[J].J Physiol,524 Pt 2:565-579.
Irwin DE,Milsom I,Hunskaar S,et al.2006.Population-based survey of urinary incontinence,overactive bladder,and other lower urinary tract symptoms in five countries:results of the EPIC study[J].Eur Urol,50:1306-1314;discussion 1314-1305.
Joseph MA,Harlow SD,Wei JT,et al.2003.Risk factors for lower urinary tract symptoms in a population-based sample of African-American men[J].Am J Epidemiol,157:906-914.
Kaplan SA,Roehrborn CG,Rovner ES,et al.2006.Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder:a randomized controlled trial[J].JAMA,296:2319-2328.
Lee JY,Kim HW,Lee SJ,et al.2004.Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder[J].BJU Int,94:817-820.
Levin R,Chichester P,Hass M,et al.2002.Obstructive bladder dysfunction:morphological, biochemical and molecular changes[J].Eur Urol Suppl,1:14-20.
Malmgren A,Sjogren C,Uvelius B,et al.1987.Cystometrical evaluation of bladder instability in rats with infravesical outflow obstruction[J].J Urol,137:1291-1294.
Nalbantgil S,Nalbantgil I,Onder R 2000.Clinically additive effect between doxazosin and amlodipine in the treatment of essential hypertension[J].Am J Hypertens,13:921-926.
NIH Management of hypertension in adults in primary care:partial update.The National Institute for Health and Clinical Excellence[online][J].Available from URL:http://www.nice.org.uk/guidance/CG34.
Nomiya M,Yamaguchi O 2003.A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders[J].J Urol,170:649-653.
Ozturk H,Onen A,Guneli E,et al.2003.Effects of methoctramine on bladder overactivity in a rat model[J].Urology,61:671-676.
Pandita RK,Persson K,Hedlund P,et al.1998.Testosterone-induced prostatic growth in the rat causes bladder overactivity unrelated to detrusor hypertrophy[J].Prostate,35:102-108.
Parsons JK 2007.Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms:new approaches to old problems[J].J Urol,178:395-401.
Pinggera GM,Mitterberger M,Pallwein L,et al.2008a.alpha-Blockers improve chronic ischaemia of the lower urinary tract in patients with lower urinary tract symptoms[J].BJU Int,101:319-324.
Pinggera GM,Mitterberger M,Steiner E,et al.2008b.Association of lower urinary tract symptoms and chronic ischaemia of the lower urinary tract in elderly women and men:assessment using colour Doppler ultrasonography[J].BJU Int,102:470-474.
Pool JL 1991.Combination antihypertensive therapy with terazosin and other antihypertensive agents:results of clinical trials[J].Am Heart J,122:926-931.
Pressler L,Santarosa R,Te A,et al.1997.The incidence of hypertension(HTN) in a population of men with benign prostatic hyperplasia(BPH):analysis based on the AUA symptom score and race[J].Urology,147(Suppl):371.
Rohrmann S,Smit E,Giovannucci E,et al.2005.Association between markers of the metabolic syndrome and lower urinary tract symptoms in the Third National Health and Nutrition Examination Survey(NHANES III)[J].Int J Obes(Lond),29:310-316.
Rosen R,Altwein J,Boyle P,et al.2003.Lower urinary tract symptoms and male sexual dysfunction:the multinational survey of the aging male(MSAM-7)[J].Eur Urol,44:637-649.
Rud T,Andersson KE,Ulmsten U 1979.Effects of nifedipine in women with unstable bladders[J]. Urol Int,34:421-429.
Sica DA 2002.Rationale for fixed-dose combinations in the treatment of hypertension:the cycle repeats[J].Drugs,62:443-462.
Smith MS,Schambra UB,Wilson KH,et al.1999.Alpha 1-adrenergic receptors in human spinal cord:specific localized expression of mRNA encoding alpha 1-adrenergic receptor subtypes at four distinct levels[J].Brain Res Mol Brain Res,63:254-261.
Sugaya K,Nishijima S,Miyazato M,et al.2002.Effects of intrathecal injection of tamsulosin and
naftopidil,alpha-1A and-1D adrenergic receptor antagonists,on bladder activity in rats[J].Neurosci Lett,328:74-76.
Tatemichi S,Akiyama K,Kobayashi M,et al.2006.A selective alpha1A-adrenoceptor antagonist inhibits detrusor overactivity in a rat model of benign prostatic hyperplasia[J].J Urol,176:1236-1241.
Taylor JA,Hand GA,Johnson DG,et al.1992.Augmented forearm vasoconstriction during dynamic exercise in healthy older men[J].Circulation,86:1789-1799.
Teramoto N,Yunoki T,Ikawa S,et al.2001.The involvement of L-type Ca(2+) channels in the relaxant effects of the ATP-sensitive K(+) channel opener ZD6169 on pig urethral smooth muscle[J].Br J Pharmacol,134:1505-1515.
Wegener JW,Schulla V,Lee TS,et al.2004.An essential role of Cav1.2 L-type calcium channel for urinary bladder function[J].FASEB J,18:1159-1161.
Whitworth JA 2003.2003 World Health Organization(WHO)/International Society of Hypertension(ISH) statement on management of hypertension[J].J Hypertens,21:1983-1992.
Wong SY,Woo J,Hong A,et al.2006.Risk factors for lower urinary tract symptoms in southern Chinese men[J].Urology,68:1009-1014.
Wu C,Sui G,Fry CH 2002.The role of the L-type Ca(2+) channel in refilling functional intracellular Ca(2+) stores in guinea-pig detrusor smooth muscle[J].J Physiol,538:357-369.
Yang Y,Zhao XF,Li HZ,et al.2007.Efficacy and safety of combined therapy with terazosin and tolteradine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia:a prospective study[J].Chin Med J(Engl),120:370-374.
Achari R,Hosmane B,Bonacci E,et al.2000.The relationship between terazosin dose and blood pressure response in hypertensive patients[J].J Clin Pharmacol,40:1166-1172.
Anderson KE 1993.Pharmacology of lower urinary tract smooth muscles and penile erectile tissues[J].Pharmacol Rev,45:253-308.
Aso Y,Homma Y 1995.Clinical research criteria:response criteria for evaluating efficacy of treatments for benign prostatic hypertrophy[J].Br J Urol,76 Suppl 1:69-73.
AUA 2006.Management of BPH clinical guideline.2003.Updated 2006.http://www.auanet.org/guidelines/bph.cfm.
Badawi JK,Li H,Langbein S,et al.2006.Inhibitory effects of L-and T-type calcium antagonists on contractions of human detrusor muscle[J].Eur J Clin Pharmacol,62:347-354.
Chappie CR,Roehrborn CG 2006.A shifted paradigm for the further understanding,evaluation,and treatment of lower urinary tract symptoms in men:focus on the bladder[J].Eur Urol,49:651-658.
Chobanian AV,Bakris GL,Black HR,et al.2003.Seventh report of the Joint National Committee on Prevention,Detection,Evaluation,and Treatment of High Blood Pressure[J].Hypertension,42:1206-1252.
CUA 2007.Chinese Urological Association Guidelines on Managements of urinary diseases.Available at:http://www.cuan.cn/cnspro/WebDiseaseGuide.aspx.
EAU 2004.EAU guidelines on benign prostatic hyperplasia.http://www.uroweb.org/fileadmin/user_upload/Guidelines/BPH.pdf.
Eckert RE,Schreier U,Drescher P,et al.1995.Regulation of prostatic smooth muscle contractility by intracellular second messengers:implications for the conservative treatment of benign prostatic hyperplasia[J].Urol Int,54:6-21.
ESH-ESC 2003.European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension[J].J Hypertens,21:1011-1053.
Fovaeus M,Andersson KE,Batra S,et al.1987.Effects of calcium,calcium channel blockers and Bay K 8644 on contractions induced by muscarinic receptor stimulation of isolated bladder muscle from rabbit and man[J].J Urol,137:798-803.
Ganitkevich VY,Isenberg G 1992.Contribution of Ca(2+)-induced Ca2+ release to the[Ca2+]i transients in myocytes from guinea-pig urinary bladder[J].J Physiol,458:119-137.
Gu D,Gupta A,Muntner P,et al.2005.Prevalence of cardiovascular disease risk factor clustering among the adult population of China:results from the International Collaborative Study of Cardiovascular Disease in Asia(InterAsia)[J].Circulation,112:658-665.
Hashitani H,Bramich NJ,Hirst GD 2000.Mechanisms of excitatory neuromuscular transmission in the guinea-pig urinary bladder[J].J Physiol,524 Pt 2:565-579.
Hosmane BS,Maurath CJ,Jordan DC,et al.1992.Effect of age and dose on the incidence of adverse events in the treatment of hypertension in patients receiving terazosin[J].J Clin Pharmacol,32:434-443.
Itskovitz HD 1994.Alpha 1-blockade for the treatment of hypertension:a megastudy of terazosin in 2214 clinical practice settings[J].Clin Ther,16:490-504.
Joseph MA,Harlow SD,Wei JT,et al.2003.Risk factors for lower urinary tract symptoms in a population-based sample of African-American men[J].Am J Epidemiol,157:906-914.
Kaplan SA,Roehrborn CG,Rovner ES,et al.2006.Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder:a randomized controlled trial[J].JAMA,296:2319-2328.
Lee JY,Kim HW,Lee SJ,et al.2004.Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder[J].BJU Int,94:817-820.
Lenz ML,Pool JL,Laddu AR,et al.1995.Combined terazosin and verapamil therapy in essential hypertension.Hemodynamic and pharmacokinetic interactions[J].Am J Hypertens,8:133-145.
Nalbantgil S,Nalbantgil I,Onder R 2000.Clinically additive effect between doxazosin and amlodipine in the treatment of essential hypertension[J].Am J Hypertens,13:921-926.
Parsons JK 2007.Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms:new approaches to old problems[J].J Urol,178:395-401.
Peili G,X C,H L,et al.2000.Clinical study of domestic terazosin on benign prostatic hyperplasia[J].Chin J Clin Pharmacol,16:338-341.
Pool JL 1991.Combination antihypertensive therapy with terazosin and other antihypertensive agents:results of clinical trials[J].Am Heart J,122:926-931.
Rohrmann S,Smit E,Giovannucci E,et al.2005.Association between markers of the metabolic syndrome and lower urinary tract symptoms in the Third National Health and Nutrition Examination Survey(NHANES Ⅲ)[J].Int J Obes(Lond),29:310-316.
Rosen R,Altwein J,Boyle P,et al.2003.Lower urinary tract symptoms and male sexual dysfunction:the multinational survey of the aging male(MSAM-7)[J].Eur Urol,44:637-649.
Tanaka Y,Masumori N,Itoh N,et al.2002.Urodynamic effects of terazosin treatment for Japanese patients with symptomatic benign prostatic hyperplasia[J].J Urol,167:2492-2495.
Teramoto N,Yunoki T,Ikawa S,et al.2001.The involvement of L-type Ca(2+) channels in the relaxant effects of the ATP-sensitive K(+) channel opener ZD6169 on pig urethral smooth muscle[J].Br J Pharmacol,134:1505-1515.
Thorpe A,Neal D 2003.Benign prostatic hyperplasia[J].Lancet,361:1359-1367.
Titmarsh S,Monk JP 1987.Terazosin.A review of its pharmacodynamic and pharmacokinetic properties,and therapeutic efficacy in essential hypertension[J].Drugs,33:461-477.
Tsujii T 2000.Comparison of prazosin,terazosin and tamsulosin in the treatment of symptomatic benign prostatic hyperplasia:a short-term open,randomized multicenter study.BPH Medical Therapy Study Group.Benign prostatic hyperplasia[J].Int J Urol,7:199-205.
Valle R,Semplicini A,Serena L,et al.1994.[Pressure and metabolic effects of terazosin in essential hypertension][J].Cardiologia,39:421-424.
Wegener JW,Schulla V,Lee TS,et al.2004.An essential role of Cav1.2 L-type calcium channel for urinary bladder function[J].FASEB J,18:1159-1161.
Wong SY,Woo J,Hong A,et al.2006.Risk factors for lower urinary tract symptoms in southern Chinese men[J].Urology,68:1009-1014.
Wu C,Sui G,Fry CH 2002.The role of the L-type Ca(2+) channel in refilling functional intracellular Ca(2+) stores in guinea-pig detrusor smooth muscle[J].J Physiol,538:357-369.
Wykretowicz A,Guzik P,Wysocki H 2008.Doxazosin in the current treatment of hypertension[J].Expert Opin Pharmacother,9:625-633.
Xu X,Niu T,Christiani DC,et al.1997.Environmental and occupational determinants of blood pressure in rural communities in China[J].Ann Epidemiol,7:95-106.
Yang Y,Zhao XF,Li HZ,et al.2007.Efficacy and safety of combined therapy with terazosin and tolteradine for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia:a prospective study[J].Chin Med J(Engl),120:370-374.
Zusman RM 2000.The role of alpha 1-blockers in combination therapy for hypertension[J].Int J Clin Pract,54:36-40.